Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation

<!DOCTYPE html> <html lang="en" xmlns:og="http://ogp.me/ns#" xmlns:fb="https://www.facebook.com/2008/fbml"> <head> <meta charset="utf-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge,chrome=1"> <meta content="mdpi" name="sso-service" /> <meta content="width=device-width, initial-scale=1.0" name="viewport" /> <title>Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer</title><link rel="stylesheet" href="https://pub.mdpi-res.com/assets/css/font-awesome.min.css?eb190a3a77e5e1ee?1739771134"> <link rel="stylesheet" href="https://pub.mdpi-res.com/assets/css/jquery.multiselect.css?f56c135cbf4d1483?1739771134"> <link rel="stylesheet" href="https://pub.mdpi-res.com/assets/css/chosen.min.css?d7ca5ca9441ef9e1?1739771134"> <link rel="stylesheet" href="https://pub.mdpi-res.com/assets/css/main2.css?6398b1425402cd8f?1739771134"> <link rel="mask-icon" href="https://pub.mdpi-res.com/img/mask-icon-128.svg?c1c7eca266cd7013?1739771134" color="#4f5671"> <link rel="apple-touch-icon" sizes="180x180" href="https://pub.mdpi-res.com/icon/apple-touch-icon-180x180.png?1739771134"> <link rel="apple-touch-icon" sizes="152x152" href="https://pub.mdpi-res.com/icon/apple-touch-icon-152x152.png?1739771134"> <link rel="apple-touch-icon" sizes="144x144" href="https://pub.mdpi-res.com/icon/apple-touch-icon-144x144.png?1739771134"> <link rel="apple-touch-icon" sizes="120x120" href="https://pub.mdpi-res.com/icon/apple-touch-icon-120x120.png?1739771134"> <link rel="apple-touch-icon" sizes="114x114" href="https://pub.mdpi-res.com/icon/apple-touch-icon-114x114.png?1739771134"> <link rel="apple-touch-icon" sizes="76x76" href="https://pub.mdpi-res.com/icon/apple-touch-icon-76x76.png?1739771134"> <link rel="apple-touch-icon" sizes="72x72" href="https://pub.mdpi-res.com/icon/apple-touch-icon-72x72.png?1739771134"> <link rel="apple-touch-icon" sizes="57x57" href="https://pub.mdpi-res.com/icon/apple-touch-icon-57x57.png?1739771134"> <link rel="apple-touch-icon" href="https://pub.mdpi-res.com/icon/apple-touch-icon-57x57.png?1739771134"> <link rel="apple-touch-icon-precomposed" href="https://pub.mdpi-res.com/icon/apple-touch-icon-57x57.png?1739771134"> <link rel="manifest" href="/manifest.json"> <meta name="theme-color" content="#ffffff"> <meta name="application-name" content=" "/> <link rel="apple-touch-startup-image" href="https://pub.mdpi-res.com/img/journals/cancers-logo-sq.png?8600e93ff98dbf14"> <link rel="apple-touch-icon" href="https://pub.mdpi-res.com/img/journals/cancers-logo-sq.png?8600e93ff98dbf14"> <meta name="msapplication-TileImage" content="https://pub.mdpi-res.com/img/journals/cancers-logo-sq.png?8600e93ff98dbf14"> <link rel="stylesheet" href="https://pub.mdpi-res.com/assets/css/jquery-ui-1.10.4.custom.min.css?80647d88647bf347?1739771134"> <link rel="stylesheet" href="https://pub.mdpi-res.com/assets/css/magnific-popup.min.css?04d343e036f8eecd?1739771134"> <link rel="stylesheet" href="https://pub.mdpi-res.com/assets/css/xml2html/article-html.css?230b005b39af4260?1739771134"> <style> h2, #abstract .related_suggestion_title { } .batch_articles a { color: #000; } a, .batch_articles .authors a, a:focus, a:hover, a:active, .batch_articles a:focus, .batch_articles a:hover, li.side-menu-li a { } span.label a { color: #fff; } #main-content a.title-link:hover, #main-content a.title-link:focus, #main-content div.generic-item a.title-link:hover, #main-content div.generic-item a.title-link:focus { } #main-content #middle-column .generic-item.article-item a.title-link:hover, #main-content #middle-column .generic-item.article-item a.title-link:focus { } .art-authors a.toEncode { color: #333; font-weight: 700; } #main-content #middle-column ul li::before { } .accordion-navigation.active a.accordion__title, .accordion-navigation.active a.accordion__title::after { } .accordion-navigation li:hover::before, .accordion-navigation li:hover a, .accordion-navigation li:focus a { } .relative-size-container .relative-size-image .relative-size { } .middle-column__help__fixed a:hover i, } input[type="checkbox"]:checked:after { } input[type="checkbox"]:not(:disabled):hover:before { } #main-content .bolded-text { } #main-content .hypothesis-count-container { } #main-content .hypothesis-count-container:before { } .full-size-menu ul li.menu-item .dropdown-wrapper { } .full-size-menu ul li.menu-item > a.open::after { } #title-story .title-story-orbit .orbit-caption { #background: url('/img/design/000000_background.png') !important; background: url('/img/design/ffffff_background.png') !important; color: rgb(51, 51, 51) !important; } #main-content .content__container__orbit { background-color: #000 !important; } #main-content .content__container__journal { color: #fff; } .html-article-menu .row span { } .html-article-menu .row span.active { } .accordion-navigation__journal .side-menu-li.active::before, .accordion-navigation__journal .side-menu-li.active a { color: rgba(26,59,132,0.75) !important; font-weight: 700; } .accordion-navigation__journal .side-menu-li:hover::before , .accordion-navigation__journal .side-menu-li:hover a { color: rgba(26,59,132,0.75) !important; } .side-menu-ul li.active a, .side-menu-ul li.active, .side-menu-ul li.active::before { color: rgba(26,59,132,0.75) !important; } .side-menu-ul li.active a { } .result-selected, .active-result.highlighted, .active-result:hover, .result-selected, .active-result.highlighted, .active-result:focus { } .search-container.search-container__default-scheme { } nav.tab-bar .open-small-search.active:after { } .search-container.search-container__default-scheme .custom-accordion-for-small-screen-link::after { color: #fff; } @media only screen and (max-width: 50em) { #main-content .content__container.journal-info { color: #fff; } #main-content .content__container.journal-info a { color: #fff; } } .button.button--color { } .button.button--color:hover, .button.button--color:focus { } .button.button--color-journal { position: relative; background-color: rgba(26,59,132,0.75); border-color: #fff; color: #fff !important; } .button.button--color-journal:hover::before { content: ''; position: absolute; top: 0; left: 0; height: 100%; width: 100%; background-color: #ffffff; opacity: 0.2; } .button.button--color-journal:visited, .button.button--color-journal:hover, .button.button--color-journal:focus { background-color: rgba(26,59,132,0.75); border-color: #fff; color: #fff !important; } .button.button--color path { } .button.button--color:hover path { fill: #fff; } #main-content #search-refinements .ui-slider-horizontal .ui-slider-range { } .breadcrumb__element:last-of-type a { } #main-header { } #full-size-menu .top-bar, #full-size-menu li.menu-item span.user-email { } .top-bar-section li:not(.has-form) a:not(.button) { } #full-size-menu li.menu-item .dropdown-wrapper li a:hover { } #full-size-menu li.menu-item a:hover, #full-size-menu li.menu.item a:focus, nav.tab-bar a:hover { } #full-size-menu li.menu.item a:active, #full-size-menu li.menu.item a.active { } #full-size-menu li.menu-item a.open-mega-menu.active, #full-size-menu li.menu-item div.mega-menu, a.open-mega-menu.active { } #full-size-menu li.menu-item div.mega-menu li, #full-size-menu li.menu-item div.mega-menu a { border-color: #9a9a9a; } div.type-section h2 { font-size: 20px; line-height: 26px; font-weight: 300; } div.type-section h3 { margin-left: 15px; margin-bottom: 0px; font-weight: 300; } .journal-tabs .tab-title.active a { } </style> <link rel="stylesheet" href="https://pub.mdpi-res.com/assets/css/slick.css?f38b2db10e01b157?1739771134"> <meta name="title" content="Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer"> <meta name="description" content="Over the last few years, immunotherapy has been considered as a key player in the treatment of solid tumors. Immune checkpoint inhibitors (ICIs) have become the breakthrough treatment, with prolonged responses and improved survival results. ICIs use the immune system to defeat cancer by breaking the axes that allow tumors to escape immune surveillance. Innate and adaptive immunity are involved in mechanisms against tumor growth. The gut microbiome and its role in such mechanisms is a relatively new study field. The presence of a high microbial variation in the gut seems to be remarkably important for the efficacy of immunotherapy, interfering with innate immunity. Metabolic and immunity pathways are related with specific gut microbiota composition. Various studies have explored the composition of gut microbiota in correlation with the effectiveness of immunotherapy. Colorectal cancer (CRC) patients have gained little benefit from immunotherapy until now. Only mismatch repair-deficient/microsatellite-unstable tumors seem to respond positively to immunotherapy. However, gut microbiota could be the key to expanding the use of immunotherapy to a greater range of CRC patients." > <link rel="image_src" href="https://pub.mdpi-res.com/img/journals/cancers-logo.png?8600e93ff98dbf14" > <meta name="dc.title" content="Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer"> <meta name="dc.creator" content="Asimina Koulouridi"> <meta name="dc.creator" content="Ippokratis Messaritakis"> <meta name="dc.creator" content="Nikolaos Gouvas"> <meta name="dc.creator" content="John Tsiaoussis"> <meta name="dc.creator" content="John Souglakos"> <meta name="dc.type" content="Review"> <meta name="dc.source" content="Cancers 2021, Vol. 13, Page 43"> <meta name="dc.date" content="2020-12-25"> <meta name ="dc.identifier" content="10.3390/cancers13010043"> <meta name="dc.publisher" content="Multidisciplinary Digital Publishing Institute"> <meta name="dc.rights" content="http://creativecommons.org/licenses/by/3.0/"> <meta name="dc.format" content="application/pdf" > <meta name="dc.language" content="en" > <meta name="dc.description" content="Over the last few years, immunotherapy has been considered as a key player in the treatment of solid tumors. Immune checkpoint inhibitors (ICIs) have become the breakthrough treatment, with prolonged responses and improved survival results. ICIs use the immune system to defeat cancer by breaking the axes that allow tumors to escape immune surveillance. Innate and adaptive immunity are involved in mechanisms against tumor growth. The gut microbiome and its role in such mechanisms is a relatively new study field. The presence of a high microbial variation in the gut seems to be remarkably important for the efficacy of immunotherapy, interfering with innate immunity. Metabolic and immunity pathways are related with specific gut microbiota composition. Various studies have explored the composition of gut microbiota in correlation with the effectiveness of immunotherapy. Colorectal cancer (CRC) patients have gained little benefit from immunotherapy until now. Only mismatch repair-deficient/microsatellite-unstable tumors seem to respond positively to immunotherapy. However, gut microbiota could be the key to expanding the use of immunotherapy to a greater range of CRC patients." > <meta name="dc.subject" content="immunotherapy" > <meta name="dc.subject" content="immune checkpoint inhibitors" > <meta name="dc.subject" content="gut microbiota" > <meta name="dc.subject" content="colorectal cancer" > <meta name ="prism.issn" content="2072-6694"> <meta name ="prism.publicationName" content="Cancers"> <meta name ="prism.publicationDate" content="2020-12-25"> <meta name ="prism.volume" content="13"> <meta name ="prism.number" content="1"> <meta name ="prism.section" content="Review" > <meta name ="prism.startingPage" content="43" > <meta name="citation_issn" content="2072-6694"> <meta name="citation_journal_title" content="Cancers"> <meta name="citation_publisher" content="Multidisciplinary Digital Publishing Institute"> <meta name="citation_title" content="Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer"> <meta name="citation_publication_date" content="2021/1"> <meta name="citation_online_date" content="2020/12/25"> <meta name="citation_volume" content="13"> <meta name="citation_issue" content="1"> <meta name="citation_firstpage" content="43"> <meta name="citation_author" content="Koulouridi, Asimina"> <meta name="citation_author" content="Messaritakis, Ippokratis"> <meta name="citation_author" content="Gouvas, Nikolaos"> <meta name="citation_author" content="Tsiaoussis, John"> <meta name="citation_author" content="Souglakos, John"> <meta name="citation_doi" content="10.3390/cancers13010043"> <meta name="citation_id" content="mdpi-cancers13010043"> <meta name="citation_abstract_html_url" content="https://www.mdpi.com/2072-6694/13/1/43"> <meta name="citation_pdf_url" content="https://www.mdpi.com/2072-6694/13/1/43/pdf?version=1608994987"> <link rel="alternate" type="application/pdf" title="PDF Full-Text" href="https://www.mdpi.com/2072-6694/13/1/43/pdf?version=1608994987"> <meta name="fulltext_pdf" content="https://www.mdpi.com/2072-6694/13/1/43/pdf?version=1608994987"> <meta name="citation_fulltext_html_url" content="https://www.mdpi.com/2072-6694/13/1/43/htm"> <link rel="alternate" type="text/html" title="HTML Full-Text" href="https://www.mdpi.com/2072-6694/13/1/43/htm"> <meta name="fulltext_html" content="https://www.mdpi.com/2072-6694/13/1/43/htm"> <link rel="alternate" type="text/xml" title="XML Full-Text" href="https://www.mdpi.com/2072-6694/13/1/43/xml"> <meta name="fulltext_xml" content="https://www.mdpi.com/2072-6694/13/1/43/xml"> <meta name="citation_xml_url" content="https://www.mdpi.com/2072-6694/13/1/43/xml"> <meta name="twitter:card" content="summary" /> <meta name="twitter:site" content="@MDPIOpenAccess" /> <meta name="twitter:image" content="https://pub.mdpi-res.com/img/journals/cancers-logo-social.png?8600e93ff98dbf14" /> <meta property="fb:app_id" content="131189377574"/> <meta property="og:site_name" content="MDPI"/> <meta property="og:type" content="article"/> <meta property="og:url" content="https://www.mdpi.com/2072-6694/13/1/43" /> <meta property="og:title" content="Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer" /> <meta property="og:description" content="Over the last few years, immunotherapy has been considered as a key player in the treatment of solid tumors. Immune checkpoint inhibitors (ICIs) have become the breakthrough treatment, with prolonged responses and improved survival results. ICIs use the immune system to defeat cancer by breaking the axes that allow tumors to escape immune surveillance. Innate and adaptive immunity are involved in mechanisms against tumor growth. The gut microbiome and its role in such mechanisms is a relatively new study field. The presence of a high microbial variation in the gut seems to be remarkably important for the efficacy of immunotherapy, interfering with innate immunity. Metabolic and immunity pathways are related with specific gut microbiota composition. Various studies have explored the composition of gut microbiota in correlation with the effectiveness of immunotherapy. Colorectal cancer (CRC) patients have gained little benefit from immunotherapy until now. Only mismatch repair-deficient/microsatellite-unstable tumors seem to respond positively to immunotherapy. However, gut microbiota could be the key to expanding the use of immunotherapy to a greater range of CRC patients." /> <meta property="og:image" content="https://pub.mdpi-res.com/cancers/cancers-13-00043/article_deploy/html/images/cancers-13-00043-ag-550.jpg?1608995055" /> <link rel="alternate" type="application/rss+xml" title="MDPI Publishing - Latest articles" href="https://www.mdpi.com/rss"> <meta name="google-site-verification" content="PxTlsg7z2S00aHroktQd57fxygEjMiNHydKn3txhvwY"> <meta name="facebook-domain-verification" content="mcoq8dtq6sb2hf7z29j8w515jjoof7" /> <script id="Cookiebot" data-cfasync="false" src="https://consent.cookiebot.com/uc.js" data-cbid="51491ddd-fe7a-4425-ab39-69c78c55829f" type="text/javascript" async></script>  <script type="text/plain" data-cookieconsent="statistics"> (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start': new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src= 'https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f); })(window,document,'script','dataLayer','GTM-WPK7SW5'); </script> <script type="text/plain" data-cookieconsent="statistics"> _linkedin_partner_id = "2846186"; window._linkedin_data_partner_ids = window._linkedin_data_partner_ids || []; window._linkedin_data_partner_ids.push(_linkedin_partner_id); </script><script type="text/javascript"> (function(){var s = document.getElementsByTagName("script")[0]; var b = document.createElement("script"); b.type = "text/javascript";b.async = true; b.src = "https://snap.licdn.com/li.lms-analytics/insight.min.js"; s.parentNode.insertBefore(b, s);})(); </script> <script type="text/plain" data-cookieconsent="statistics" data-cfasync="false" src="//script.crazyegg.com/pages/scripts/0116/4951.js" async="async" ></script> </head> <body> <div class="direction direction_right" id="small_right" style="border-right-width: 0px; padding:0;"> <i class="fa fa-caret-right fa-2x"></i> </div> <div class="big_direction direction_right" id="big_right" style="border-right-width: 0px;"> <div style="text-align: right;"> Next Article in Journal<br> <div><a href="/2072-6694/13/1/44">HER2 Status in High-Risk Endometrial Cancers (PORTEC-3): Relationship with Histotype, Molecular Classification, and Clinical Outcomes</a></div> Next Article in Special Issue<br> <div><a href="/2072-6694/13/1/131">Immune Checkpoint Inhibitors for the Treatment of Bladder Cancer</a></div> </div> </div> <div class="direction" id="small_left" style="border-left-width: 0px"> <i class="fa fa-caret-left fa-2x"></i> </div> <div class="big_direction" id="big_left" style="border-left-width: 0px;"> <div> Previous Article in Journal<br> <div><a href="/2072-6694/13/1/42">The Nuclear Pore Complex and mRNA Export in Cancer</a></div> Previous Article in Special Issue<br> <div><a href="/2072-6694/12/10/2872">The Antidiabetic Agent Acarbose Improves Anti-PD-1 and Rapamycin Efficacy in Preclinical Renal Cancer</a></div> </div> </div> <div style="clear: both;"></div> <div id="menuModal" class="reveal-modal reveal-modal-new reveal-modal-menu" aria-hidden="true" data-reveal role="dialog"> <div class="menu-container"> <div class="UI_NavMenu"> <div class="content__container " > <div class="custom-accordion-for-small-screen-link " > <h2>Journals</h2> </div> <div class="target-item custom-accordion-for-small-screen-content show-for-medium-up"> <div class="menu-container__links"> <div style="width: 100%; float: left;"> <a href="/about/journals">Active Journals</a> <a href="/about/journalfinder">Find a Journal</a> <a href="/about/journals/proposal">Journal Proposal</a> <a href="/about/proceedings">Proceedings Series</a> </div> </div> </div> </div> <a href="/topics"> <h2>Topics</h2> </a> <div class="content__container " > <div class="custom-accordion-for-small-screen-link " > <h2>Information</h2> </div> <div class="target-item custom-accordion-for-small-screen-content show-for-medium-up"> <div class="menu-container__links"> <div style="width: 100%; max-width: 200px; float: left;"> <a href="/authors">For Authors</a> <a href="/reviewers">For Reviewers</a> <a href="/editors">For Editors</a> <a href="/librarians">For Librarians</a> <a href="/publishing_services">For Publishers</a> <a href="/societies">For Societies</a> <a href="/conference_organizers">For Conference Organizers</a> </div> <div style="width: 100%; max-width: 250px; float: left;"> <a href="/openaccess">Open Access Policy</a> <a href="/ioap">Institutional Open Access Program</a> <a href="/special_issues_guidelines">Special Issues Guidelines</a> <a href="/editorial_process">Editorial Process</a> <a href="/ethics">Research and Publication Ethics</a> <a href="/apc">Article Processing Charges</a> <a href="/awards">Awards</a> <a href="/testimonials">Testimonials</a> </div> </div> </div> </div> <a href="/authors/english"> <h2>Author Services</h2> </a> <div class="content__container " > <div class="custom-accordion-for-small-screen-link " > <h2>Initiatives</h2> </div> <div class="target-item custom-accordion-for-small-screen-content show-for-medium-up"> <div class="menu-container__links"> <div style="width: 100%; float: left;"> <a href="https://sciforum.net" target="_blank" rel="noopener noreferrer">Sciforum</a> <a href="https://www.mdpi.com/books" target="_blank" rel="noopener noreferrer">MDPI Books</a> <a href="https://www.preprints.org" target="_blank" rel="noopener noreferrer">Preprints.org</a> <a href="https://www.scilit.com" target="_blank" rel="noopener noreferrer">Scilit</a> <a href="https://sciprofiles.com" target="_blank" rel="noopener noreferrer">SciProfiles</a> <a href="https://encyclopedia.pub" target="_blank" rel="noopener noreferrer">Encyclopedia</a> <a href="https://jams.pub" target="_blank" rel="noopener noreferrer">JAMS</a> <a href="/about/proceedings">Proceedings Series</a> </div> </div> </div> </div> <div class="content__container " > <div class="custom-accordion-for-small-screen-link " > <h2>About</h2> </div> <div class="target-item custom-accordion-for-small-screen-content show-for-medium-up"> <div class="menu-container__links"> <div style="width: 100%; float: left;"> <a href="/about">Overview</a> <a href="/about/contact">Contact</a> <a href="https://careers.mdpi.com" target="_blank" rel="noopener noreferrer">Careers</a> <a href="/about/announcements">News</a> <a href="/about/press">Press</a> <a href="http://blog.mdpi.com/" target="_blank" rel="noopener noreferrer">Blog</a> </div> </div> </div> </div> </div> <div class="menu-container__buttons"> <a class="button UA_SignInUpButton" href="/user/login">Sign In / Sign Up</a> </div> </div> </div> <div id="captchaModal" class="reveal-modal reveal-modal-new reveal-modal-new--small" data-reveal aria-label="Captcha" aria-hidden="true" role="dialog"></div> <div id="actionDisabledModal" class="reveal-modal" data-reveal aria-labelledby="actionDisableModalTitle" aria-hidden="true" role="dialog" style="width: 300px;"> <h2 id="actionDisableModalTitle">Notice</h2> <form action="/email/captcha" method="post" id="emailCaptchaForm"> <div class="row"> <div id="js-action-disabled-modal-text" class="small-12 columns"> </div> <div id="js-action-disabled-modal-submit" class="small-12 columns" style="margin-top: 10px; display: none;"> You can make submissions to other journals <a href="https://susy.mdpi.com/user/manuscripts/upload">here</a>. </div> </div> </form> <a class="close-reveal-modal" aria-label="Close"> <i class="material-icons">clear</i> </a> </div> <div id="rssNotificationModal" class="reveal-modal reveal-modal-new" data-reveal aria-labelledby="rssNotificationModalTitle" aria-hidden="true" role="dialog"> <div class="row"> <div class="small-12 columns"> <h2 id="rssNotificationModalTitle">Notice</h2> <p> You are accessing a machine-readable page. In order to be human-readable, please install an RSS reader. </p> </div> </div> <div class="row"> <div class="small-12 columns"> <a class="button button--color js-rss-notification-confirm">Continue</a> <a class="button button--grey" onclick="$(this).closest('.reveal-modal').find('.close-reveal-modal').click(); return false;">Cancel</a> </div> </div> <a class="close-reveal-modal" aria-label="Close"> <i class="material-icons">clear</i> </a> </div> <div id="drop-article-label-openaccess" class="f-dropdown medium" data-dropdown-content aria-hidden="true" tabindex="-1"> <p> All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited. For more information, please refer to <a href="https://www.mdpi.com/openaccess">https://www.mdpi.com/openaccess</a>. </p> </div> <div id="drop-article-label-feature" class="f-dropdown medium" data-dropdown-content aria-hidden="true" tabindex="-1"> <p> Feature papers represent the most advanced research with significant potential for high impact in the field. A Feature Paper should be a substantial original Article that involves several techniques or approaches, provides an outlook for future research directions and describes possible research applications. </p> <p> Feature papers are submitted upon individual invitation or recommendation by the scientific editors and must receive positive feedback from the reviewers. </p> </div> <div id="drop-article-label-choice" class="f-dropdown medium" data-dropdown-content aria-hidden="true" tabindex="-1"> <p> Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal. <div style="margin-top: -10px;"> <div id="drop-article-label-choice-journal-link" style="display: none; margin-top: -10px; padding-top: 10px;"> </div> </div> </p> </div> <div id="drop-article-label-resubmission" class="f-dropdown medium" data-dropdown-content aria-hidden="true" tabindex="-1"> <p> Original Submission Date Received: <span id="drop-article-label-resubmission-date"></span>. </p> </div> <div id="container"> <noscript> <div id="no-javascript"> You seem to have javascript disabled. Please note that many of the page functionalities won't work as expected without javascript enabled. </div> </noscript> <div class="fixed"> <nav class="tab-bar show-for-medium-down"> <div class="row full-width collapse"> <div class="medium-3 small-4 columns"> <a href="/"> <img class="full-size-menu__mdpi-logo" src="https://pub.mdpi-res.com/img/design/mdpi-pub-logo-black-small1.svg?da3a8dcae975a41c?1739771134" style="width: 64px;" title="MDPI Open Access Journals"> </a> </div> <div class="medium-3 small-4 columns right-aligned"> <div class="show-for-medium-down"> <a href="#" style="display: none;"> <i class="material-icons" onclick="$('#menuModal').foundation('reveal', 'close'); return false;">clear</i> </a> <a class="js-toggle-desktop-layout-link" title="Toggle desktop layout" style="display: none;" href="/toggle_desktop_layout_cookie"> <i class="material-icons">zoom_out_map</i> </a> <a href="#" class="js-open-small-search open-small-search"> <i class="material-icons show-for-small only">search</i> </a> <a title="MDPI main page" class="js-open-menu" data-reveal-id="menuModal" href="#"> <i class="material-icons">menu</i> </a> </div> </div> </div> </nav> </div> <section class="main-section"> <header> <div class="full-size-menu show-for-large-up"> <div class="row full-width"> <div class="large-1 columns"> <a href="/"> <img class="full-size-menu__mdpi-logo" src="https://pub.mdpi-res.com/img/design/mdpi-pub-logo-black-small1.svg?da3a8dcae975a41c?1739771134" title="MDPI Open Access Journals"> </a> </div> <div class="large-8 columns text-right UI_NavMenu"> <ul> <li class="menu-item"> <a href="/about/journals" data-dropdown="journals-dropdown" aria-controls="journals-dropdown" aria-expanded="false" data-options="is_hover: true; hover_timeout: 200">Journals</a> <ul id="journals-dropdown" class="f-dropdown dropdown-wrapper dropdown-wrapper__small" data-dropdown-content aria-hidden="true" tabindex="-1"> <li> <div class="row"> <div class="small-12 columns"> <ul> <li> <a href="/about/journals"> Active Journals </a> </li> <li> <a href="/about/journalfinder"> Find a Journal </a> </li> <li> <a href="/about/journals/proposal"> Journal Proposal </a> </li> <li> <a href="/about/proceedings"> Proceedings Series </a> </li> </ul> </div> </div> </li> </ul> </li> <li class="menu-item"> <a href="/topics">Topics</a> </li> <li class="menu-item"> <a href="/authors" data-dropdown="information-dropdown" aria-controls="information-dropdown" aria-expanded="false" data-options="is_hover:true; hover_timeout:200">Information</a> <ul id="information-dropdown" class="f-dropdown dropdown-wrapper" data-dropdown-content aria-hidden="true" tabindex="-1"> <li> <div class="row"> <div class="small-5 columns right-border"> <ul> <li> <a href="/authors">For Authors</a> </li> <li> <a href="/reviewers">For Reviewers</a> </li> <li> <a href="/editors">For Editors</a> </li> <li> <a href="/librarians">For Librarians</a> </li> <li> <a href="/publishing_services">For Publishers</a> </li> <li> <a href="/societies">For Societies</a> </li> <li> <a href="/conference_organizers">For Conference Organizers</a> </li> </ul> </div> <div class="small-7 columns"> <ul> <li> <a href="/openaccess">Open Access Policy</a> </li> <li> <a href="/ioap">Institutional Open Access Program</a> </li> <li> <a href="/special_issues_guidelines">Special Issues Guidelines</a> </li> <li> <a href="/editorial_process">Editorial Process</a> </li> <li> <a href="/ethics">Research and Publication Ethics</a> </li> <li> <a href="/apc">Article Processing Charges</a> </li> <li> <a href="/awards">Awards</a> </li> <li> <a href="/testimonials">Testimonials</a> </li> </ul> </div> </div> </li> </ul> </li> <li class="menu-item"> <a href="/authors/english">Author Services</a> </li> <li class="menu-item"> <a href="/about/initiatives" data-dropdown="initiatives-dropdown" aria-controls="initiatives-dropdown" aria-expanded="false" data-options="is_hover: true; hover_timeout: 200">Initiatives</a> <ul id="initiatives-dropdown" class="f-dropdown dropdown-wrapper dropdown-wrapper__small" data-dropdown-content aria-hidden="true" tabindex="-1"> <li> <div class="row"> <div class="small-12 columns"> <ul> <li> <a href="https://sciforum.net" target="_blank" rel="noopener noreferrer"> Sciforum </a> </li> <li> <a href="https://www.mdpi.com/books" target="_blank" rel="noopener noreferrer"> MDPI Books </a> </li> <li> <a href="https://www.preprints.org" target="_blank" rel="noopener noreferrer"> Preprints.org </a> </li> <li> <a href="https://www.scilit.com" target="_blank" rel="noopener noreferrer"> Scilit </a> </li> <li> <a href="https://sciprofiles.com" target="_blank" rel="noopener noreferrer"> SciProfiles </a> </li> <li> <a href="https://encyclopedia.pub" target="_blank" rel="noopener noreferrer"> Encyclopedia </a> </li> <li> <a href="https://jams.pub" target="_blank" rel="noopener noreferrer"> JAMS </a> </li> <li> <a href="/about/proceedings"> Proceedings Series </a> </li> </ul> </div> </div> </li> </ul> </li> <li class="menu-item"> <a href="/about" data-dropdown="about-dropdown" aria-controls="about-dropdown" aria-expanded="false" data-options="is_hover: true; hover_timeout: 200">About</a> <ul id="about-dropdown" class="f-dropdown dropdown-wrapper dropdown-wrapper__small" data-dropdown-content aria-hidden="true" tabindex="-1"> <li> <div class="row"> <div class="small-12 columns"> <ul> <li> <a href="/about"> Overview </a> </li> <li> <a href="/about/contact"> Contact </a> </li> <li> <a href="https://careers.mdpi.com" target="_blank" rel="noopener noreferrer"> Careers </a> </li> <li> <a href="/about/announcements"> News </a> </li> <li> <a href="/about/press"> Press </a> </li> <li> <a href="http://blog.mdpi.com/" target="_blank" rel="noopener noreferrer"> Blog </a> </li> </ul> </div> </div> </li> </ul> </li> </ul> </div> <div class="large-3 columns text-right full-size-menu__buttons"> <div> <a class="button button--default-inversed UA_SignInUpButton" href="/user/login">Sign In / Sign Up</a> <a class="button button--default js-journal-active-only-link js-journal-active-only-submit-link UC_NavSubmitButton" href=" https://susy.mdpi.com/user/manuscripts/upload?journal=cancers " data-disabledmessage="new submissions are not possible.">Submit</a> </div> </div> </div> </div> <div class="header-divider"> </div> <div class="search-container hide-for-small-down row search-container__homepage-scheme"> <form id="basic_search" style="background-color: inherit !important;" class="large-12 medium-12 columns " action="/search" method="get"> <div class="row search-container__main-elements"> <div class="large-2 medium-2 small-12 columns text-right1 small-only-text-left"> <div class="show-for-medium-up"> <div class="search-input-label"> </div> </div> <span class="search-container__title">Search<span class="hide-for-medium"> for Articles</span><span class="hide-for-small">:</span></span> </div> <div class="custom-accordion-for-small-screen-content"> <div class="large-2 medium-2 small-6 columns "> <div class=""> <div class="search-input-label">Title / Keyword</div> </div> <input type="text" placeholder="Title / Keyword" id="q" tabindex="1" name="q" value="" /> </div> <div class="large-2 medium-2 small-6 columns "> <div class=""> <div class="search-input-label">Author / Affiliation / Email</div> </div> <input type="text" id="authors" placeholder="Author / Affiliation / Email" tabindex="2" name="authors" value="" /> </div> <div class="large-2 medium-2 small-6 columns "> <div class=""> <div class="search-input-label">Journal</div> </div> <select id="journal" tabindex="3" name="journal" class="chosen-select"> <option value="">All Journals</option> <option value="acoustics" > Acoustics </option> <option value="amh" > Acta Microbiologica Hellenica (AMH) </option> <option value="actuators" > Actuators </option> <option value="adhesives" > Adhesives </option> <option value="admsci" > Administrative Sciences </option> <option value="adolescents" > Adolescents </option> <option value="arm" > Advances in Respiratory Medicine (ARM) </option> <option value="aerobiology" > Aerobiology </option> <option value="aerospace" > Aerospace </option> <option value="agriculture" > Agriculture </option> <option value="agriengineering" > AgriEngineering </option> <option value="agrochemicals" > Agrochemicals </option> <option value="agronomy" > Agronomy </option> <option value="ai" > AI </option> <option value="aisens" > AI Sensors </option> <option value="air" > Air </option> <option value="algorithms" > Algorithms </option> <option value="allergies" > Allergies </option> <option value="alloys" > Alloys </option> <option value="analytica" > Analytica </option> <option value="analytics" > Analytics </option> <option value="anatomia" > Anatomia </option> <option value="anesthres" > Anesthesia Research </option> <option value="animals" > Animals </option> <option value="antibiotics" > Antibiotics </option> <option value="antibodies" > Antibodies </option> <option value="antioxidants" > Antioxidants </option> <option value="applbiosci" > Applied Biosciences </option> <option value="applmech" > Applied Mechanics </option> <option value="applmicrobiol" > Applied Microbiology </option> <option value="applnano" > Applied Nano </option> <option value="applsci" > Applied Sciences </option> <option value="asi" > Applied System Innovation (ASI) </option> <option value="appliedchem" > AppliedChem </option> <option value="appliedmath" > AppliedMath </option> <option value="aquacj" > Aquaculture Journal </option> <option value="architecture" > Architecture </option> <option value="arthropoda" > Arthropoda </option> <option value="arts" > Arts </option> <option value="astronomy" > Astronomy </option> <option value="atmosphere" > Atmosphere </option> <option value="atoms" > Atoms </option> <option value="audiolres" > Audiology Research </option> <option value="automation" > Automation </option> <option value="axioms" > Axioms </option> <option value="bacteria" > Bacteria </option> <option value="batteries" > Batteries </option> <option value="behavsci" > Behavioral Sciences </option> <option value="beverages" > Beverages </option> <option value="BDCC" > Big Data and Cognitive Computing (BDCC) </option> <option value="biochem" > BioChem </option> <option value="bioengineering" > Bioengineering </option> <option value="biologics" > Biologics </option> <option value="biology" > Biology </option> <option value="blsf" > Biology and Life Sciences Forum </option> <option value="biomass" > Biomass </option> <option value="biomechanics" > Biomechanics </option> <option value="biomed" > BioMed </option> <option value="biomedicines" > Biomedicines </option> <option value="biomedinformatics" > BioMedInformatics </option> <option value="biomimetics" > Biomimetics </option> <option value="biomolecules" > Biomolecules </option> <option value="biophysica" > Biophysica </option> <option value="biosensors" > Biosensors </option> <option value="biosphere" > Biosphere </option> <option value="biotech" > BioTech </option> <option value="birds" > Birds </option> <option value="blockchains" > Blockchains </option> <option value="brainsci" > Brain Sciences </option> <option value="buildings" > Buildings </option> <option value="businesses" > Businesses </option> <option value="carbon" > C (Journal of Carbon Research) </option> <option value="cancers" selected='selected'> Cancers </option> <option value="cardiogenetics" > Cardiogenetics </option> <option value="catalysts" > Catalysts </option> <option value="cells" > Cells </option> <option value="ceramics" > Ceramics </option> <option value="challenges" > Challenges </option> <option value="ChemEngineering" > ChemEngineering </option> <option value="chemistry" > Chemistry </option> <option value="chemproc" > Chemistry Proceedings </option> <option value="chemosensors" > Chemosensors </option> <option value="children" > Children </option> <option value="chips" > Chips </option> <option value="civileng" > CivilEng </option> <option value="cleantechnol" > Clean Technologies (Clean Technol.) </option> <option value="climate" > Climate </option> <option value="ctn" > Clinical and Translational Neuroscience (CTN) </option> <option value="clinbioenerg" > Clinical Bioenergetics </option> <option value="clinpract" > Clinics and Practice </option> <option value="clockssleep" > Clocks & Sleep </option> <option value="coasts" > Coasts </option> <option value="coatings" > Coatings </option> <option value="colloids" > Colloids and Interfaces </option> <option value="colorants" > Colorants </option> <option value="commodities" > Commodities </option> <option value="complications" > Complications </option> <option value="compounds" > Compounds </option> <option value="computation" > Computation </option> <option value="csmf" > Computer Sciences & Mathematics Forum </option> <option value="computers" > Computers </option> <option value="condensedmatter" > Condensed Matter </option> <option value="conservation" > Conservation </option> <option value="constrmater" > Construction Materials </option> <option value="cmd" > Corrosion and Materials Degradation (CMD) </option> <option value="cosmetics" > Cosmetics </option> <option value="covid" > COVID </option> <option value="cmtr" > Craniomaxillofacial Trauma & Reconstruction (CMTR) </option> <option value="crops" > Crops </option> <option value="cryo" > Cryo </option> <option value="cryptography" > Cryptography </option> <option value="crystals" > Crystals </option> <option value="cimb" > Current Issues in Molecular Biology (CIMB) </option> <option value="curroncol" > Current Oncology </option> <option value="dairy" > Dairy </option> <option value="data" > Data </option> <option value="dentistry" > Dentistry Journal </option> <option value="dermato" > Dermato </option> <option value="dermatopathology" > Dermatopathology </option> <option value="designs" > Designs </option> <option value="diabetology" > Diabetology </option> <option value="diagnostics" > Diagnostics </option> <option value="dietetics" > Dietetics </option> <option value="digital" > Digital </option> <option value="disabilities" > Disabilities </option> <option value="diseases" > Diseases </option> <option value="diversity" > Diversity </option> <option value="dna" > DNA </option> <option value="drones" > Drones </option> <option value="ddc" > Drugs and Drug Candidates (DDC) </option> <option value="dynamics" > Dynamics </option> <option value="earth" > Earth </option> <option value="ecologies" > Ecologies </option> <option value="econometrics" > Econometrics </option> <option value="economies" > Economies </option> <option value="education" > Education Sciences </option> <option value="electricity" > Electricity </option> <option value="electrochem" > Electrochem </option> <option value="electronicmat" > Electronic Materials </option> <option value="electronics" > Electronics </option> <option value="ecm" > Emergency Care and Medicine </option> <option value="encyclopedia" > Encyclopedia </option> <option value="endocrines" > Endocrines </option> <option value="energies" > Energies </option> <option value="esa" > Energy Storage and Applications (ESA) </option> <option value="eng" > Eng </option> <option value="engproc" > Engineering Proceedings </option> <option value="entropy" > Entropy </option> <option value="eesp" > Environmental and Earth Sciences Proceedings </option> <option value="environments" > Environments </option> <option value="epidemiologia" > Epidemiologia </option> <option value="epigenomes" > Epigenomes </option> <option value="ebj" > European Burn Journal (EBJ) </option> <option value="ejihpe" > European Journal of Investigation in Health, Psychology and Education (EJIHPE) </option> <option value="fermentation" > Fermentation </option> <option value="fibers" > Fibers </option> <option value="fintech" > FinTech </option> <option value="fire" > Fire </option> <option value="fishes" > Fishes </option> <option value="fluids" > Fluids </option> <option value="foods" > Foods </option> <option value="forecasting" > Forecasting </option> <option value="forensicsci" > Forensic Sciences </option> <option value="forests" > Forests </option> <option value="fossstud" > Fossil Studies </option> <option value="foundations" > Foundations </option> <option value="fractalfract" > Fractal and Fractional (Fractal Fract) </option> <option value="fuels" > Fuels </option> <option value="future" > Future </option> <option value="futureinternet" > Future Internet </option> <option value="futurepharmacol" > Future Pharmacology </option> <option value="futuretransp" > Future Transportation </option> <option value="galaxies" > Galaxies </option> <option value="games" > Games </option> <option value="gases" > Gases </option> <option value="gastroent" > Gastroenterology Insights </option> <option value="gastrointestdisord" > Gastrointestinal Disorders </option> <option value="gastronomy" > Gastronomy </option> <option value="gels" > Gels </option> <option value="genealogy" > Genealogy </option> <option value="genes" > Genes </option> <option value="geographies" > Geographies </option> <option value="geohazards" > GeoHazards </option> <option value="geomatics" > Geomatics </option> <option value="geometry" > Geometry </option> <option value="geosciences" > Geosciences </option> <option value="geotechnics" > Geotechnics </option> <option value="geriatrics" > Geriatrics </option> <option value="glacies" > Glacies </option> <option value="gucdd" > Gout, Urate, and Crystal Deposition Disease (GUCDD) </option> <option value="grasses" > Grasses </option> <option value="greenhealth" > Green Health </option> <option value="hardware" > Hardware </option> <option value="healthcare" > Healthcare </option> <option value="hearts" > Hearts </option> <option value="hemato" > Hemato </option> <option value="hematolrep" > Hematology Reports </option> <option value="heritage" > Heritage </option> <option value="histories" > Histories </option> <option value="horticulturae" > Horticulturae </option> <option value="hospitals" > Hospitals </option> <option value="humanities" > Humanities </option> <option value="humans" > Humans </option> <option value="hydrobiology" > Hydrobiology </option> <option value="hydrogen" > Hydrogen </option> <option value="hydrology" > Hydrology </option> <option value="hygiene" > Hygiene </option> <option value="immuno" > Immuno </option> <option value="idr" > Infectious Disease Reports </option> <option value="informatics" > Informatics </option> <option value="information" > Information </option> <option value="infrastructures" > Infrastructures </option> <option value="inorganics" > Inorganics </option> <option value="insects" > Insects </option> <option value="instruments" > Instruments </option> <option value="iic" > Intelligent Infrastructure and Construction </option> <option value="ijerph" > International Journal of Environmental Research and Public Health (IJERPH) </option> <option value="ijfs" > International Journal of Financial Studies (IJFS) </option> <option value="ijms" > International Journal of Molecular Sciences (IJMS) </option> <option value="IJNS" > International Journal of Neonatal Screening (IJNS) </option> <option value="ijom" > International Journal of Orofacial Myology and Myofunctional Therapy (IJOM) </option> <option value="ijpb" > International Journal of Plant Biology (IJPB) </option> <option value="ijt" > International Journal of Topology </option> <option value="ijtm" > International Journal of Translational Medicine (IJTM) </option> <option value="ijtpp" > International Journal of Turbomachinery, Propulsion and Power (IJTPP) </option> <option value="ime" > International Medical Education (IME) </option> <option value="inventions" > Inventions </option> <option value="IoT" > IoT </option> <option value="ijgi" > ISPRS International Journal of Geo-Information (IJGI) </option> <option value="J" > J </option> <option value="jal" > Journal of Ageing and Longevity (JAL) </option> <option value="jcdd" > Journal of Cardiovascular Development and Disease (JCDD) </option> <option value="jcto" > Journal of Clinical & Translational Ophthalmology (JCTO) </option> <option value="jcm" > Journal of Clinical Medicine (JCM) </option> <option value="jcs" > Journal of Composites Science (J. Compos. Sci.) </option> <option value="jcp" > Journal of Cybersecurity and Privacy (JCP) </option> <option value="jdad" > Journal of Dementia and Alzheimer's Disease (JDAD) </option> <option value="jdb" > Journal of Developmental Biology (JDB) </option> <option value="jeta" > Journal of Experimental and Theoretical Analyses (JETA) </option> <option value="jemr" > Journal of Eye Movement Research (JEMR) </option> <option value="jfb" > Journal of Functional Biomaterials (JFB) </option> <option value="jfmk" > Journal of Functional Morphology and Kinesiology (JFMK) </option> <option value="jof" > Journal of Fungi (JoF) </option> <option value="jimaging" > Journal of Imaging (J. Imaging) </option> <option value="jintelligence" > Journal of Intelligence (J. Intell.) </option> <option value="jlpea" > Journal of Low Power Electronics and Applications (JLPEA) </option> <option value="jmmp" > Journal of Manufacturing and Materials Processing (JMMP) </option> <option value="jmse" > Journal of Marine Science and Engineering (JMSE) </option> <option value="jmahp" > Journal of Market Access & Health Policy (JMAHP) </option> <option value="jmms" > Journal of Mind and Medical Sciences (JMMS) </option> <option value="jmp" > Journal of Molecular Pathology (JMP) </option> <option value="jnt" > Journal of Nanotheranostics (JNT) </option> <option value="jne" > Journal of Nuclear Engineering (JNE) </option> <option value="ohbm" > Journal of Otorhinolaryngology, Hearing and Balance Medicine (JOHBM) </option> <option value="jop" > Journal of Parks </option> <option value="jpm" > Journal of Personalized Medicine (JPM) </option> <option value="jpbi" > Journal of Pharmaceutical and BioTech Industry (JPBI) </option> <option value="jor" > Journal of Respiration (JoR) </option> <option value="jrfm" > Journal of Risk and Financial Management (JRFM) </option> <option value="jsan" > Journal of Sensor and Actuator Networks (JSAN) </option> <option value="joma" > Journal of the Oman Medical Association (JOMA) </option> <option value="jtaer" > Journal of Theoretical and Applied Electronic Commerce Research (JTAER) </option> <option value="jvd" > Journal of Vascular Diseases (JVD) </option> <option value="jox" > Journal of Xenobiotics (JoX) </option> <option value="jzbg" > Journal of Zoological and Botanical Gardens (JZBG) </option> <option value="journalmedia" > Journalism and Media </option> <option value="kidneydial" > Kidney and Dialysis </option> <option value="kinasesphosphatases" > Kinases and Phosphatases </option> <option value="knowledge" > Knowledge </option> <option value="labmed" > LabMed </option> <option value="laboratories" > Laboratories </option> <option value="land" > Land </option> <option value="languages" > Languages </option> <option value="laws" > Laws </option> <option value="life" > Life </option> <option value="limnolrev" > Limnological Review </option> <option value="lipidology" > Lipidology </option> <option value="liquids" > Liquids </option> <option value="literature" > Literature </option> <option value="livers" > Livers </option> <option value="logics" > Logics </option> <option value="logistics" > Logistics </option> <option value="lubricants" > Lubricants </option> <option value="lymphatics" > Lymphatics </option> <option value="make" > Machine Learning and Knowledge Extraction (MAKE) </option> <option value="machines" > Machines </option> <option value="macromol" > Macromol </option> <option value="magnetism" > Magnetism </option> <option value="magnetochemistry" > Magnetochemistry </option> <option value="marinedrugs" > Marine Drugs </option> <option value="materials" > Materials </option> <option value="materproc" > Materials Proceedings </option> <option value="mca" > Mathematical and Computational Applications (MCA) </option> <option value="mathematics" > Mathematics </option> <option value="medsci" > Medical Sciences </option> <option value="msf" > Medical Sciences Forum </option> <option value="medicina" > Medicina </option> <option value="medicines" > Medicines </option> <option value="membranes" > Membranes </option> <option value="merits" > Merits </option> <option value="metabolites" > Metabolites </option> <option value="metals" > Metals </option> <option value="meteorology" > Meteorology </option> <option value="methane" > Methane </option> <option value="mps" > Methods and Protocols (MPs) </option> <option value="metrics" > Metrics </option> <option value="metrology" > Metrology </option> <option value="micro" > Micro </option> <option value="microbiolres" > Microbiology Research </option> <option value="micromachines" > Micromachines </option> <option value="microorganisms" > Microorganisms </option> <option value="microplastics" > Microplastics </option> <option value="microwave" > Microwave </option> <option value="minerals" > Minerals </option> <option value="mining" > Mining </option> <option value="modelling" > Modelling </option> <option value="mmphys" > Modern Mathematical Physics </option> <option value="molbank" > Molbank </option> <option value="molecules" > Molecules </option> <option value="mti" > Multimodal Technologies and Interaction (MTI) </option> <option value="muscles" > Muscles </option> <option value="nanoenergyadv" > Nanoenergy Advances </option> <option value="nanomanufacturing" > Nanomanufacturing </option> <option value="nanomaterials" > Nanomaterials </option> <option value="ndt" > NDT </option> <option value="network" > Network </option> <option value="neuroglia" > Neuroglia </option> <option value="neurolint" > Neurology International </option> <option value="neurosci" > NeuroSci </option> <option value="nitrogen" > Nitrogen </option> <option value="ncrna" > Non-Coding RNA (ncRNA) </option> <option value="nursrep" > Nursing Reports </option> <option value="nutraceuticals" > Nutraceuticals </option> <option value="nutrients" > Nutrients </option> <option value="obesities" > Obesities </option> <option value="oceans" > Oceans </option> <option value="onco" > Onco </option> <option value="optics" > Optics </option> <option value="oral" > Oral </option> <option value="organics" > Organics </option> <option value="organoids" > Organoids </option> <option value="osteology" > Osteology </option> <option value="oxygen" > Oxygen </option> <option value="parasitologia" > Parasitologia </option> <option value="particles" > Particles </option> <option value="pathogens" > Pathogens </option> <option value="pathophysiology" > Pathophysiology </option> <option value="pediatrrep" > Pediatric Reports </option> <option value="pets" > Pets </option> <option value="pharmaceuticals" > Pharmaceuticals </option> <option value="pharmaceutics" > Pharmaceutics </option> <option value="pharmacoepidemiology" > Pharmacoepidemiology </option> <option value="pharmacy" > Pharmacy </option> <option value="philosophies" > Philosophies </option> <option value="photochem" > Photochem </option> <option value="photonics" > Photonics </option> <option value="phycology" > Phycology </option> <option value="physchem" > Physchem </option> <option value="psf" > Physical Sciences Forum </option> <option value="physics" > Physics </option> <option value="physiologia" > Physiologia </option> <option value="plants" > Plants </option> <option value="plasma" > Plasma </option> <option value="platforms" > Platforms </option> <option value="pollutants" > Pollutants </option> <option value="polymers" > Polymers </option> <option value="polysaccharides" > Polysaccharides </option> <option value="populations" > Populations </option> <option value="poultry" > Poultry </option> <option value="powders" > Powders </option> <option value="proceedings" > Proceedings </option> <option value="processes" > Processes </option> <option value="prosthesis" > Prosthesis </option> <option value="proteomes" > Proteomes </option> <option value="psychiatryint" > Psychiatry International </option> <option value="psychoactives" > Psychoactives </option> <option value="psycholint" > Psychology International </option> <option value="publications" > Publications </option> <option value="qubs" > Quantum Beam Science (QuBS) </option> <option value="quantumrep" > Quantum Reports </option> <option value="quaternary" > Quaternary </option> <option value="radiation" > Radiation </option> <option value="reactions" > Reactions </option> <option value="realestate" > Real Estate </option> <option value="receptors" > Receptors </option> <option value="recycling" > Recycling </option> <option value="rsee" > Regional Science and Environmental Economics (RSEE) </option> <option value="religions" > Religions </option> <option value="remotesensing" > Remote Sensing </option> <option value="reports" > Reports </option> <option value="reprodmed" > Reproductive Medicine (Reprod. Med.) </option> <option value="resources" > Resources </option> <option value="rheumato" > Rheumato </option> <option value="risks" > Risks </option> <option value="robotics" > Robotics </option> <option value="ruminants" > Ruminants </option> <option value="safety" > Safety </option> <option value="sci" > Sci </option> <option value="scipharm" > Scientia Pharmaceutica (Sci. Pharm.) </option> <option value="sclerosis" > Sclerosis </option> <option value="seeds" > Seeds </option> <option value="sensors" > Sensors </option> <option value="separations" > Separations </option> <option value="sexes" > Sexes </option> <option value="signals" > Signals </option> <option value="sinusitis" > Sinusitis </option> <option value="smartcities" > Smart Cities </option> <option value="socsci" > Social Sciences </option> <option value="siuj" > Société Internationale d’Urologie Journal (SIUJ) </option> <option value="societies" > Societies </option> <option value="software" > Software </option> <option value="soilsystems" > Soil Systems </option> <option value="solar" > Solar </option> <option value="solids" > Solids </option> <option value="spectroscj" > Spectroscopy Journal </option> <option value="sports" > Sports </option> <option value="standards" > Standards </option> <option value="stats" > Stats </option> <option value="stresses" > Stresses </option> <option value="surfaces" > Surfaces </option> <option value="surgeries" > Surgeries </option> <option value="std" > Surgical Techniques Development </option> <option value="sustainability" > Sustainability </option> <option value="suschem" > Sustainable Chemistry </option> <option value="symmetry" > Symmetry </option> <option value="synbio" > SynBio </option> <option value="systems" > Systems </option> <option value="targets" > Targets </option> <option value="taxonomy" > Taxonomy </option> <option value="technologies" > Technologies </option> <option value="telecom" > Telecom </option> <option value="textiles" > Textiles </option> <option value="thalassrep" > Thalassemia Reports </option> <option value="therapeutics" > Therapeutics </option> <option value="thermo" > Thermo </option> <option value="timespace" > Time and Space </option> <option value="tomography" > Tomography </option> <option value="tourismhosp" > Tourism and Hospitality </option> <option value="toxics" > Toxics </option> <option value="toxins" > Toxins </option> <option value="transplantology" > Transplantology </option> <option value="traumacare" > Trauma Care </option> <option value="higheredu" > Trends in Higher Education </option> <option value="tropicalmed" > Tropical Medicine and Infectious Disease (TropicalMed) </option> <option value="universe" > Universe </option> <option value="urbansci" > Urban Science </option> <option value="uro" > Uro </option> <option value="vaccines" > Vaccines </option> <option value="vehicles" > Vehicles </option> <option value="venereology" > Venereology </option> <option value="vetsci" > Veterinary Sciences </option> <option value="vibration" > Vibration </option> <option value="virtualworlds" > Virtual Worlds </option> <option value="viruses" > Viruses </option> <option value="vision" > Vision </option> <option value="waste" > Waste </option> <option value="water" > Water </option> <option value="wild" > Wild </option> <option value="wind" > Wind </option> <option value="women" > Women </option> <option value="world" > World </option> <option value="wevj" > World Electric Vehicle Journal (WEVJ) </option> <option value="youth" > Youth </option> <option value="zoonoticdis" > Zoonotic Diseases </option> </select> </div> <div class="large-2 medium-2 small-6 columns "> <div class=""> <div class="search-input-label">Article Type</div> </div> <select id="article_type" tabindex="4" name="article_type" class="chosen-select"> <option value="">All Article Types</option> <option value="research-article">Article</option> <option value="review-article">Review</option> <option value="rapid-communication">Communication</option> <option value="editorial">Editorial</option> <option value="abstract">Abstract</option> <option value="book-review">Book Review</option> <option value="brief-communication">Brief Communication</option> <option value="brief-report">Brief Report</option> <option value="case-report">Case Report</option> <option value="clinicopathological-challenge">Clinicopathological Challenge</option> <option value="article-commentary">Comment</option> <option value="commentary">Commentary</option> <option value="concept-paper">Concept Paper</option> <option value="conference-report">Conference Report</option> <option value="correction">Correction</option> <option value="creative">Creative</option> <option value="data-descriptor">Data Descriptor</option> <option value="discussion">Discussion</option> <option value="Entry">Entry</option> <option value="essay">Essay</option> <option value="expression-of-concern">Expression of Concern</option> <option value="extended-abstract">Extended Abstract</option> <option value="field-guide">Field Guide</option> <option value="giants-in-urology">Giants in Urology</option> <option value="guidelines">Guidelines</option> <option value="hypothesis">Hypothesis</option> <option value="interesting-image">Interesting Images</option> <option value="letter">Letter</option> <option value="books-received">New Book Received</option> <option value="obituary">Obituary</option> <option value="opinion">Opinion</option> <option value="perspective">Perspective</option> <option value="proceedings">Proceeding Paper</option> <option value="project-report">Project Report</option> <option value="protocol">Protocol</option> <option value="registered-report">Registered Report</option> <option value="reply">Reply</option> <option value="retraction">Retraction</option> <option value="note">Short Note</option> <option value="study-protocol">Study Protocol</option> <option value="systematic_review">Systematic Review</option> <option value="technical-note">Technical Note</option> <option value="tutorial">Tutorial</option> <option value="urology-around-the-world">Urology around the World</option> <option value="viewpoint">Viewpoint</option> </select> </div> <div class="large-1 medium-1 small-6 end columns small-push-6 medium-reset-order large-reset-order js-search-collapsed-button-container"> <div class="search-input-label"> </div> <input type="submit" id="search" value="Search" class="button button--dark button--full-width searchButton1 US_SearchButton" tabindex="12"> </div> <div class="large-1 medium-1 small-6 end columns large-text-left small-only-text-center small-pull-6 medium-reset-order large-reset-order js-search-collapsed-link-container"> <div class="search-input-label"> </div> <a class="main-search-clear search-container__link" href="#" onclick="openAdvanced(''); return false;">Advanced<span class="show-for-small-only"> Search</span></a> </div> </div> </div> <div class="search-container__advanced" style="margin-top: 0; padding-top: 0px; background-color: inherit; color: inherit;"> <div class="row"> <div class="large-2 medium-2 columns show-for-medium-up"> </div> <div class="large-2 medium-2 small-6 columns "> <div class=""> <div class="search-input-label">Section</div> </div> <select id="section" tabindex="5" name="section" class="chosen-select"> <option value=""></option> </select> </div> <div class="large-2 medium-2 small-6 columns "> <div class=""> <div class="search-input-label">Special Issue</div> </div> <select id="special_issue" tabindex="6" name="special_issue" class="chosen-select"> <option value=""></option> </select> </div> <div class="large-1 medium-1 small-6 end columns "> <div class="search-input-label">Volume</div> <input type="text" id="volume" tabindex="7" name="volume" placeholder="..." value="13" /> </div> <div class="large-1 medium-1 small-6 end columns "> <div class="search-input-label">Issue</div> <input type="text" id="issue" tabindex="8" name="issue" placeholder="..." value="1" /> </div> <div class="large-1 medium-1 small-6 end columns "> <div class="search-input-label">Number</div> <input type="text" id="number" tabindex="9" name="number" placeholder="..." value="" /> </div> <div class="large-1 medium-1 small-6 end columns "> <div class="search-input-label">Page</div> <input type="text" id="page" tabindex="10" name="page" placeholder="..." value="" /> </div> <div class="large-1 medium-1 small-6 columns small-push-6 medium-reset order large-reset-order medium-reset-order js-search-expanded-button-container"></div> <div class="large-1 medium-1 small-6 columns large-text-left small-only-text-center small-pull-6 medium-reset-order large-reset-order js-search-expanded-link-container"></div> </div> </div> </form> <form id="advanced-search" class="large-12 medium-12 columns"> <div class="search-container__advanced"> <div id="advanced-search-template" class="row advanced-search-row"> <div class="large-2 medium-2 small-12 columns show-for-medium-up"> </div> <div class="large-2 medium-2 small-3 columns connector-div"> <div class="search-input-label"><span class="show-for-medium-up">Logical Operator</span><span class="show-for-small">Operator</span></div> <select class="connector"> <option value="and">AND</option> <option value="or">OR</option> </select> </div> <div class="large-3 medium-3 small-6 columns search-text-div"> <div class="search-input-label">Search Text</div> <input type="text" class="search-text" placeholder="Search text"> </div> <div class="large-2 medium-2 small-6 large-offset-0 medium-offset-0 small-offset-3 columns search-field-div"> <div class="search-input-label">Search Type</div> <select class="search-field"> <option value="all">All fields</option> <option value="title">Title</option> <option value="abstract">Abstract</option> <option value="keywords">Keywords</option> <option value="authors">Authors</option> <option value="affiliations">Affiliations</option> <option value="doi">Doi</option> <option value="full_text">Full Text</option> <option value="references">References</option> </select> </div> <div class="large-1 medium-1 small-3 columns"> <div class="search-input-label"> </div> <div class="search-action-div"> <div class="search-plus"> <i class="material-icons">add_circle_outline</i> </div> </div> <div class="search-action-div"> <div class="search-minus"> <i class="material-icons">remove_circle_outline</i> </div> </div> </div> <div class="large-1 medium-1 small-6 large-offset-0 medium-offset-0 small-offset-3 end columns"> <div class="search-input-label"> </div> <input class="advanced-search-button button button--dark search-submit" type="submit" value="Search"> </div> <div class="large-1 medium-1 small-6 end columns show-for-medium-up"></div> </div> </div> </form> </div> <div class="header-divider"> </div> <div class="breadcrumb row full-row"> <div class="breadcrumb__element"> <a href="/about/journals">Journals</a> </div> <div class="breadcrumb__element"> <a href="/journal/cancers">Cancers</a> </div> <div class="breadcrumb__element"> <a href="/2072-6694/13">Volume 13</a> </div> <div class="breadcrumb__element"> <a href="/2072-6694/13/1">Issue 1</a> </div> <div class="breadcrumb__element"> <a href="#">10.3390/cancers13010043</a> </div> </div> </header> <div id="main-content" class=""> <div class="row full-width row-fixed-left-column"> <div id="left-column" class="content__column large-3 medium-3 small-12 columns"> <div class="content__container"> <a href="/journal/cancers"> <img src="https://pub.mdpi-res.com/img/journals/cancers-logo.png?8600e93ff98dbf14" alt="cancers-logo" title="Cancers" style="max-height: 60px; margin: 0 0 0 0;"> </a> <div class="generic-item no-border"> <a class="button button--color button--full-width js-journal-active-only-link js-journal-active-only-submit-link UC_ArticleSubmitButton" href="https://susy.mdpi.com/user/manuscripts/upload?form%5Bjournal_id%5D%3D23" data-disabledmessage="creating new submissions is not possible."> Submit to this Journal </a> <a class="button button--color button--full-width js-journal-active-only-link UC_ArticleReviewButton" href="https://susy.mdpi.com/volunteer/journals/review" data-disabledmessage="volunteering as journal reviewer is not possible."> Review for this Journal </a> <a class="button button--color-inversed button--color-journal button--full-width js-journal-active-only-link UC_ArticleEditIssueButton" href="/journalproposal/sendproposalspecialissue/cancers" data-path="/2072-6694/13/1/43" data-disabledmessage="proposing new special issue is not possible."> Propose a Special Issue </a> </div> <div class="generic-item link-article-menu show-for-small"> <a href="#" class="link-article-menu show-for-small"> <span class="closed">►</span> <span class="open" style="display: none;">▼</span> Article Menu </a> </div> <div class="hide-small-down-initially UI_ArticleMenu"> <div class="generic-item"> <h2>Article Menu</h2> </div> <ul class="accordion accordion__menu" data-accordion data-options="multi_expand:true;toggleable: true"> <li class="accordion-direct-link"> <a href="/2072-6694/13/1/43/scifeed_display" data-reveal-id="scifeed-modal" data-reveal-ajax="true">Subscribe SciFeed</a> </li> <li class="accordion-direct-link js-article-similarity-container" style="display: none"> <a href="#" class="js-similarity-related-articles">Recommended Articles</a> </li> <li class="accordion-navigation"> <a href="#related" class="accordion__title">Related Info Links</a> <div id="related" class="content UI_ArticleMenu_RelatedLinks"> <ul> <li class="li-link"> <a href="http://www.ncbi.nlm.nih.gov/sites/entrez/33375686" target="_blank" rel="noopener noreferrer">PubMed/Medline</a> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Immunotherapy%20in%20Solid%20Tumors%20and%20Gut%20Microbiota%3A%20The%20Correlation%E2%80%94A%20Special%20Reference%20to%20Colorectal%20Cancer" target="_blank" rel="noopener noreferrer">Google Scholar</a> </li> </ul> </div> </li> <li class="accordion-navigation"> <a href="#authors" class="accordion__title">More by Authors Links</a> <div id="authors" class="content UI_ArticleMenu_AuthorsLinks"> <ul class="side-menu-ul"> <li> <a class="expand" onclick='$(this).closest("li").next("div").toggle(); return false;'>on DOAJ</a> </li> <div id="AuthorDOAJExpand" style="display:none;"> <ul class="submenu"> <li class="li-link"> <a href='http://doaj.org/search/articles?source=%7B%22query%22%3A%7B%22query_string%22%3A%7B%22query%22%3A%22%5C%22Asimina%20Koulouridi%5C%22%22%2C%22default_operator%22%3A%22AND%22%2C%22default_field%22%3A%22bibjson.author.name%22%7D%7D%7D' target="_blank" rel="noopener noreferrer">Koulouridi, A.</a> <li> </li> <li class="li-link"> <a href='http://doaj.org/search/articles?source=%7B%22query%22%3A%7B%22query_string%22%3A%7B%22query%22%3A%22%5C%22Ippokratis%20Messaritakis%5C%22%22%2C%22default_operator%22%3A%22AND%22%2C%22default_field%22%3A%22bibjson.author.name%22%7D%7D%7D' target="_blank" rel="noopener noreferrer">Messaritakis, I.</a> <li> </li> <li class="li-link"> <a href='http://doaj.org/search/articles?source=%7B%22query%22%3A%7B%22query_string%22%3A%7B%22query%22%3A%22%5C%22Nikolaos%20Gouvas%5C%22%22%2C%22default_operator%22%3A%22AND%22%2C%22default_field%22%3A%22bibjson.author.name%22%7D%7D%7D' target="_blank" rel="noopener noreferrer">Gouvas, N.</a> <li> </li> <li class="li-link"> <a href='http://doaj.org/search/articles?source=%7B%22query%22%3A%7B%22query_string%22%3A%7B%22query%22%3A%22%5C%22John%20Tsiaoussis%5C%22%22%2C%22default_operator%22%3A%22AND%22%2C%22default_field%22%3A%22bibjson.author.name%22%7D%7D%7D' target="_blank" rel="noopener noreferrer">Tsiaoussis, J.</a> <li> </li> <li class="li-link"> <a href='http://doaj.org/search/articles?source=%7B%22query%22%3A%7B%22query_string%22%3A%7B%22query%22%3A%22%5C%22John%20Souglakos%5C%22%22%2C%22default_operator%22%3A%22AND%22%2C%22default_field%22%3A%22bibjson.author.name%22%7D%7D%7D' target="_blank" rel="noopener noreferrer">Souglakos, J.</a> <li> </li> </ul> </div> <li> <a class="expand" onclick='$(this).closest("li").next("div").toggle(); return false;'>on Google Scholar</a> </li> <div id="AuthorGoogleExpand" style="display:none;"> <ul class="submenu"> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Asimina%20Koulouridi" target="_blank" rel="noopener noreferrer">Koulouridi, A.</a> <li> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Ippokratis%20Messaritakis" target="_blank" rel="noopener noreferrer">Messaritakis, I.</a> <li> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Nikolaos%20Gouvas" target="_blank" rel="noopener noreferrer">Gouvas, N.</a> <li> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=John%20Tsiaoussis" target="_blank" rel="noopener noreferrer">Tsiaoussis, J.</a> <li> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=John%20Souglakos" target="_blank" rel="noopener noreferrer">Souglakos, J.</a> <li> </li> </ul> </div> <li> <a class="expand" onclick='$(this).closest("li").next("div").toggle(); return false;'>on PubMed</a> </li> <div id="AuthorPubMedExpand" style="display:none;"> <ul class="submenu"> <li class="li-link"> <a href="http://www.pubmed.gov/?cmd=Search&term=Asimina%20Koulouridi" target="_blank" rel="noopener noreferrer">Koulouridi, A.</a> <li> </li> <li class="li-link"> <a href="http://www.pubmed.gov/?cmd=Search&term=Ippokratis%20Messaritakis" target="_blank" rel="noopener noreferrer">Messaritakis, I.</a> <li> </li> <li class="li-link"> <a href="http://www.pubmed.gov/?cmd=Search&term=Nikolaos%20Gouvas" target="_blank" rel="noopener noreferrer">Gouvas, N.</a> <li> </li> <li class="li-link"> <a href="http://www.pubmed.gov/?cmd=Search&term=John%20Tsiaoussis" target="_blank" rel="noopener noreferrer">Tsiaoussis, J.</a> <li> </li> <li class="li-link"> <a href="http://www.pubmed.gov/?cmd=Search&term=John%20Souglakos" target="_blank" rel="noopener noreferrer">Souglakos, J.</a> <li> </li> </ul> </div> </ul> </div> </li> </ul> <span style="display:none" id="scifeed_hidden_flag"></span> <span style="display:none" id="scifeed_subscribe_url">/ajax/scifeed/subscribe</span> </div> </div> <div class="content__container responsive-moving-container large medium active hidden" data-id="article-counters"> <div id="counts-wrapper" class="row generic-item no-border" data-equalizer> <div id="js-counts-wrapper__views" class="small-12 hide columns count-div-container"> <a href="#metrics" > <div class="count-div" data-equalizer-watch> <span class="name">Article Views</span> <span class="count view-number"></span> </div> </a> </div> <div id="js-counts-wrapper__citations" class="small-12 columns hide count-div-container"> <a href="#metrics" > <div class="count-div" data-equalizer-watch> <span class="name">Citations</span> <span class="count citations-number Var_ArticleMaxCitations">-</span> </div> </a> </div> </div> </div> <div class="content__container"> <div class="hide-small-down-initially"> <ul class="accordion accordion__menu" data-accordion data-options="multi_expand:true;toggleable: true"> <li class="accordion-navigation"> <a href="#table_of_contents" class="accordion__title">Table of Contents</a> <div id="table_of_contents" class="content active"> <div class="menu-caption" id="html-quick-links-title"></div> </div> </li> </ul> </div> </div>  <div id="pbgrd-sky"></div> <script src="https://cdn.pbgrd.com/core-mdpi.js"></script> <style>.content__container { min-width: 300px; }</style>  </div> <div id="middle-column" class="content__column large-9 medium-9 small-12 columns end middle-bordered"> <div class="middle-column__help"> <div class="middle-column__help__fixed show-for-medium-up"> <span id="js-altmetrics-donut" href="#" target="_blank" rel="noopener noreferrer" style="display: none;"> <span data-badge-type='donut' class='altmetric-embed' data-doi='10.3390/cancers13010043'></span> <span>Altmetric</span> </span> <a href="#" class="UA_ShareButton" data-reveal-id="main-share-modal" title="Share"> <i class="material-icons">share</i> <span>Share</span> </a> <a href="#" data-reveal-id="main-help-modal" title="Help"> <i class="material-icons">announcement</i> <span>Help</span> </a> <a href="javascript:void(0);" data-reveal-id="cite-modal" data-counterslink = "https://www.mdpi.com/2072-6694/13/1/43/cite" > <i class="material-icons">format_quote</i> <span>Cite</span> </a> <a href="https://sciprofiles.com/discussion-groups/public/10.3390/cancers13010043?utm_source=mpdi.com&utm_medium=publication&utm_campaign=discuss_in_sciprofiles" target="_blank" rel="noopener noreferrer" title="Discuss in Sciprofiles"> <i class="material-icons">question_answer</i> <span>Discuss in SciProfiles</span> </a> </div> <div id="main-help-modal" class="reveal-modal reveal-modal-new" data-reveal aria-labelledby="modalTitle" aria-hidden="true" role="dialog"> <div class="row"> <div class="small-12 columns"> <h2 style="margin: 0;">Need Help?</h2> </div> <div class="small-6 columns"> <h3>Support</h3> <p> Find support for a specific problem in the support section of our website. </p> <a target="_blank" href="/about/contactform" class="button button--color button--full-width"> Get Support </a> </div> <div class="small-6 columns"> <h3>Feedback</h3> <p> Please let us know what you think of our products and services. </p> <a target="_blank" href="/feedback/send" class="button button--color button--full-width"> Give Feedback </a> </div> <div class="small-6 columns end"> <h3>Information</h3> <p> Visit our dedicated information section to learn more about MDPI. </p> <a target="_blank" href="/authors" class="button button--color button--full-width"> Get Information </a> </div> </div> <a class="close-reveal-modal" aria-label="Close"> <i class="material-icons">clear</i> </a> </div> </div> <div class="middle-column__main "> <div class="page-highlight"> <style type="text/css"> img.review-status { width: 30px; } </style> <div id="jmolModal" class="reveal-modal" data-reveal aria-labelledby="Captcha" aria-hidden="true" role="dialog"> <h2>JSmol Viewer</h2> <div class="row"> <div class="small-12 columns text-center"> <iframe style="width: 520px; height: 520px;" frameborder="0" id="jsmol-content"></iframe> <div class="content"></div> </div> </div> <a class="close-reveal-modal" aria-label="Close"> <i class="material-icons">clear</i> </a> </div> <div itemscope itemtype="http://schema.org/ScholarlyArticle" id="abstract" class="abstract_div"> <div class="js-check-update-container"></div> <div class="html-content__container content__container content__container__combined-for-large__first" style="overflow: auto; position: inherit;"> <div class='html-profile-nav'> <div class='top-bar'> <div class='nav-sidebar-btn show-for-large-up' data-status='opened' > <i class='material-icons'>first_page</i> </div> <a id="js-button-download" class="button button--color-inversed" style="display: none;" href="/2072-6694/13/1/43/pdf?version=1608994987" data-name="Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer" data-journal="cancers"> <i class="material-icons custom-download"></i> Download PDF </a> <div class='nav-btn'> <i class='material-icons'>settings</i> </div> <a href="/2072-6694/13/1/43/reprints" id="js-button-reprints" class="button button--color-inversed"> Order Article Reprints </a> </div> <div class='html-article-menu'> <div class='html-first-step row'> <div class='html-font-family large-6 medium-6 small-12 columns'> <div class='row'> <div class='html-font-label large-4 medium-4 small-12 columns'> Font Type: </div> <div class='large-8 medium-8 small-12 columns'> <span class="html-article-menu-option"><i style='font-family:Arial, Arial, Helvetica, sans-serif;' data-fontfamily='Arial, Arial, Helvetica, sans-serif'>Arial</i></span> <span class="html-article-menu-option"><i style='font-family:Georgia1, Georgia, serif;' data-fontfamily='Georgia1, Georgia, serif'>Georgia</i></span> <span class="html-article-menu-option"><i style='font-family:Verdana, Verdana, Geneva, sans-serif;' data-fontfamily='Verdana, Verdana, Geneva, sans-serif' >Verdana</i></span> </div> </div> </div> <div class='html-font-resize large-6 medium-6 small-12 columns'> <div class='row'> <div class='html-font-label large-4 medium-4 small-12 columns'>Font Size:</div> <div class='large-8 medium-8 small-12 columns'> <span class="html-article-menu-option a1" data-percent="100">Aa</span> <span class="html-article-menu-option a2" data-percent="120">Aa</span> <span class="html-article-menu-option a3" data-percent="160">Aa</span> </div> </div> </div> </div> <div class='row'> <div class='html-line-space large-6 medium-6 small-12 columns'> <div class='row'> <div class='html-font-label large-4 medium-4 small-12 columns' >Line Spacing:</div> <div class='large-8 medium-8 small-12 columns'> <span class="html-article-menu-option a1" data-line-height="1.5em"> <i class="fa"></i> </span> <span class="html-article-menu-option a2" data-line-height="1.8em"> <i class="fa"></i> </span> <span class="html-article-menu-option a3" data-line-height="2.1em"> <i class="fa"></i> </span> </div> </div> </div> <div class='html-column-width large-6 medium-6 small-12 columns'> <div class='row'> <div class='html-font-label large-4 medium-4 small-12 columns' >Column Width:</div> <div class='large-8 medium-8 small-12 columns'> <span class="html-article-menu-option a1" data-column-width="20%"> <i class="fa"></i> </span> <span class="html-article-menu-option a2" data-column-width="10%"> <i class="fa"></i> </span> <span class="html-article-menu-option a3" data-column-width="0%"> <i class="fa"></i> </span> </div> </div> </div> </div> <div class='row'> <div class='html-font-bg large-6 medium-6 small-12 columns end'> <div class='row'> <div class='html-font-label large-4 medium-4 small-12 columns'>Background:</div> <div class='large-8 medium-8 small-12 columns'> <div class="html-article-menu-option html-nav-bg html-nav-bright" data-bg="bright"> <i class="fa fa-file-text"></i> </div> <div class="html-article-menu-option html-nav-bg html-nav-dark" data-bg="dark"> <i class="fa fa-file-text-o"></i> </div> <div class="html-article-menu-option html-nav-bg html-nav-creme" data-bg="creme"> <i class="fa fa-file-text"></i> </div> </div> </div> </div> </div> </div> </div> <article ><div class='html-article-content'> <span itemprop="publisher" content="Multidisciplinary Digital Publishing Institute"></span><span itemprop="url" content="https://www.mdpi.com/2072-6694/13/1/43"></span> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Review</span></div> <h1 class="title hypothesis_container" itemprop="name"> Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer </h1> <div class="art-authors hypothesis_container"> by <span class="inlineblock "><div class='profile-card-drop' data-dropdown='profile-card-drop3942589' data-options='is_hover:true, hover_timeout:5000'> Asimina Koulouridi</div><div id="profile-card-drop3942589" data-dropdown-content class="f-dropdown content profile-card-content" aria-hidden="true" tabindex="-1"><div class="profile-card__title"><div class="sciprofiles-link" style="display: inline-block"><div class="sciprofiles-link__link"><img class="sciprofiles-link__image" src="/bundles/mdpisciprofileslink/img/unknown-user.png" style="width: auto; height: 16px; border-radius: 50%;"><span class="sciprofiles-link__name">Asimina Koulouridi</span></div></div></div><div class="profile-card__buttons" style="margin-bottom: 10px;"><a href="https://sciprofiles.com/profile/author/T1pvQ2g5SWFJOElVZGhsd2h1YjlRNThxdzl2N3VZQ1Q5cDJRNTliMkJsaz0=?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name" class="button button--color-inversed" target="_blank"> SciProfiles </a><a href="https://scilit.com/scholars?q=Asimina%20Koulouridi" class="button button--color-inversed" target="_blank"> Scilit </a><a href="https://www.preprints.org/search?search1=Asimina%20Koulouridi&field1=authors" class="button button--color-inversed" target="_blank"> Preprints.org </a><a href="https://scholar.google.com/scholar?q=Asimina%20Koulouridi" class="button button--color-inversed" target="_blank" rels="noopener noreferrer"> Google Scholar </a></div></div><sup> 1</sup><span style="display: inline; margin-left: 5px;"></span><a class="toEncode emailCaptcha visibility-hidden" data-author-id="3942589" href="/cdn-cgi/l/email-protection#351a565b511856525c1a591a5058545c591845475a415056415c5a5b16050504070304050d06500556050d055305050554055004010551055004010406050d0500050d0704040d0505050c055005500153050705500556"><sup><i class="fa fa-envelope-o"></i></sup></a>, </span><span class="inlineblock "><div class='profile-card-drop' data-dropdown='profile-card-drop3942590' data-options='is_hover:true, hover_timeout:5000'> Ippokratis Messaritakis</div><div id="profile-card-drop3942590" data-dropdown-content class="f-dropdown content profile-card-content" aria-hidden="true" tabindex="-1"><div class="profile-card__title"><div class="sciprofiles-link" style="display: inline-block"><div class="sciprofiles-link__link"><img class="sciprofiles-link__image" src="/bundles/mdpisciprofileslink/img/unknown-user.png" style="width: auto; height: 16px; border-radius: 50%;"><span class="sciprofiles-link__name">Ippokratis Messaritakis</span></div></div></div><div class="profile-card__buttons" style="margin-bottom: 10px;"><a href="https://sciprofiles.com/profile/808022?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name" class="button button--color-inversed" target="_blank"> SciProfiles </a><a href="https://scilit.com/scholars?q=Ippokratis%20Messaritakis" class="button button--color-inversed" target="_blank"> Scilit </a><a href="https://www.preprints.org/search?search1=Ippokratis%20Messaritakis&field1=authors" class="button button--color-inversed" target="_blank"> Preprints.org </a><a href="https://scholar.google.com/scholar?q=Ippokratis%20Messaritakis" class="button button--color-inversed" target="_blank" rels="noopener noreferrer"> Google Scholar </a></div></div><sup> 1,*</sup><span style="display: inline; margin-left: 5px;"></span><a class="toEncode emailCaptcha visibility-hidden" data-author-id="3942590" href="/cdn-cgi/l/email-protection#16397578723b75717f397a39737b777f7a3b666479627375627f79783526262622202f267527772777262e2774242f26752672277522212622267526722221277526202677222126732774"><sup><i class="fa fa-envelope-o"></i></sup></a><a href="https://orcid.org/0000-0003-1877-500X" target="_blank" rel="noopener noreferrer"><img src="https://pub.mdpi-res.com/img/design/orcid.png?0465bc3812adeb52?1739771134" title="ORCID" style="position: relative; width: 13px; margin-left: 3px; max-width: 13px !important; height: auto; top: -5px;"></a>, </span><span class="inlineblock "><div class='profile-card-drop' data-dropdown='profile-card-drop3942591' data-options='is_hover:true, hover_timeout:5000'> Nikolaos Gouvas</div><div id="profile-card-drop3942591" data-dropdown-content class="f-dropdown content profile-card-content" aria-hidden="true" tabindex="-1"><div class="profile-card__title"><div class="sciprofiles-link" style="display: inline-block"><div class="sciprofiles-link__link"><img class="sciprofiles-link__image" src="/bundles/mdpisciprofileslink/img/unknown-user.png" style="width: auto; height: 16px; border-radius: 50%;"><span class="sciprofiles-link__name">Nikolaos Gouvas</span></div></div></div><div class="profile-card__buttons" style="margin-bottom: 10px;"><a href="https://sciprofiles.com/profile/1359362?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name" class="button button--color-inversed" target="_blank"> SciProfiles </a><a href="https://scilit.com/scholars?q=Nikolaos%20Gouvas" class="button button--color-inversed" target="_blank"> Scilit </a><a href="https://www.preprints.org/search?search1=Nikolaos%20Gouvas&field1=authors" class="button button--color-inversed" target="_blank"> Preprints.org </a><a href="https://scholar.google.com/scholar?q=Nikolaos%20Gouvas" class="button button--color-inversed" target="_blank" rels="noopener noreferrer"> Google Scholar </a></div></div><sup> 2</sup><span style="display: inline; margin-left: 5px;"></span><a class="toEncode emailCaptcha visibility-hidden" data-author-id="3942591" href="/cdn-cgi/l/email-protection#eac589848ec7898d83c586c58f878b8386c79a98859e8f899e838584c9dadadadddc8fdadfdadbdb8ededadad3dadbdb88dbd2da8cdb8ed88fdad3dad9da8cdadddad8dedada8edadbdad9"><sup><i class="fa fa-envelope-o"></i></sup></a><a href="https://orcid.org/0000-0002-6541-4226" target="_blank" rel="noopener noreferrer"><img src="https://pub.mdpi-res.com/img/design/orcid.png?0465bc3812adeb52?1739771134" title="ORCID" style="position: relative; width: 13px; margin-left: 3px; max-width: 13px !important; height: auto; top: -5px;"></a>, </span><span class="inlineblock "><div class='profile-card-drop' data-dropdown='profile-card-drop3942592' data-options='is_hover:true, hover_timeout:5000'> John Tsiaoussis</div><div id="profile-card-drop3942592" data-dropdown-content class="f-dropdown content profile-card-content" aria-hidden="true" tabindex="-1"><div class="profile-card__title"><div class="sciprofiles-link" style="display: inline-block"><div class="sciprofiles-link__link"><img class="sciprofiles-link__image" src="/bundles/mdpisciprofileslink/img/unknown-user.png" style="width: auto; height: 16px; border-radius: 50%;"><span class="sciprofiles-link__name">John Tsiaoussis</span></div></div></div><div class="profile-card__buttons" style="margin-bottom: 10px;"><a href="https://sciprofiles.com/profile/791794?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name" class="button button--color-inversed" target="_blank"> SciProfiles </a><a href="https://scilit.com/scholars?q=John%20Tsiaoussis" class="button button--color-inversed" target="_blank"> Scilit </a><a href="https://www.preprints.org/search?search1=John%20Tsiaoussis&field1=authors" class="button button--color-inversed" target="_blank"> Preprints.org </a><a href="https://scholar.google.com/scholar?q=John%20Tsiaoussis" class="button button--color-inversed" target="_blank" rels="noopener noreferrer"> Google Scholar </a></div></div><sup> 3</sup><span style="display: inline; margin-left: 5px;"></span><a class="toEncode emailCaptcha visibility-hidden" data-author-id="3942592" href="/cdn-cgi/l/email-protection#7c531f1218511f1b1553105319111d1510510c0e1308191f081513125f4c4c4c4b4b484d184d494d1e4c4d4c4b4c4b4d184c4b4f484c4d4d1e4d4b491d4d4f4c4a"><sup><i class="fa fa-envelope-o"></i></sup></a><a href="https://orcid.org/0000-0002-9892-1048" target="_blank" rel="noopener noreferrer"><img src="https://pub.mdpi-res.com/img/design/orcid.png?0465bc3812adeb52?1739771134" title="ORCID" style="position: relative; width: 13px; margin-left: 3px; max-width: 13px !important; height: auto; top: -5px;"></a> and </span><span class="inlineblock "><div class='profile-card-drop' data-dropdown='profile-card-drop3942593' data-options='is_hover:true, hover_timeout:5000'> John Souglakos</div><div id="profile-card-drop3942593" data-dropdown-content class="f-dropdown content profile-card-content" aria-hidden="true" tabindex="-1"><div class="profile-card__title"><div class="sciprofiles-link" style="display: inline-block"><div class="sciprofiles-link__link"><img class="sciprofiles-link__image" src="/profiles/1011677/thumb/John_Souglakos.jpg" style="width: auto; height: 16px; border-radius: 50%;"><span class="sciprofiles-link__name">John Souglakos</span></div></div></div><div class="profile-card__buttons" style="margin-bottom: 10px;"><a href="https://sciprofiles.com/profile/1011677?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name" class="button button--color-inversed" target="_blank"> SciProfiles </a><a href="https://scilit.com/scholars?q=John%20Souglakos" class="button button--color-inversed" target="_blank"> Scilit </a><a href="https://www.preprints.org/search?search1=John%20Souglakos&field1=authors" class="button button--color-inversed" target="_blank"> Preprints.org </a><a href="https://scholar.google.com/scholar?q=John%20Souglakos" class="button button--color-inversed" target="_blank" rels="noopener noreferrer"> Google Scholar </a></div></div><sup> 1,4,*</sup><span style="display: inline; margin-left: 5px;"></span><a class="toEncode emailCaptcha visibility-hidden" data-author-id="3942593" href="/cdn-cgi/l/email-protection#d5fab6bbb1f8b6b2bcfab9fab0b8b4bcb9f8a5a7baa1b0b6a1bcbabbf6e5e5e5e0e3b4e5e7e5e1e4ece5e0e4b3e5b1e5e3e7b4e5b1e5e2e5b7e5e6e5e3e1e1e5ece5e0e5e2"><sup><i class="fa fa-envelope-o"></i></sup></a></span> </div> <div class="nrm"></div> <span style="display:block; height:6px;"></span> <div></div> <div style="margin: 5px 0 15px 0;" class="hypothesis_container"> <div class="art-affiliations"> <div class="affiliation "> <div class="affiliation-item"><sup>1</sup></div> <div class="affiliation-name ">Laboratory of Translational Oncology, School of Medicine, University of Crete, 70013 Heraklion, Greece</div> </div> <div class="affiliation "> <div class="affiliation-item"><sup>2</sup></div> <div class="affiliation-name ">Medical School, University of Cyprus, 20537 Nicosia, Cyprus</div> </div> <div class="affiliation "> <div class="affiliation-item"><sup>3</sup></div> <div class="affiliation-name ">Department of Anatomy, School of Medicine, University of Crete, 70013 Heraklion, Greece</div> </div> <div class="affiliation "> <div class="affiliation-item"><sup>4</sup></div> <div class="affiliation-name ">Department of Medical Oncology, University Hospital of Heraklion, 71110 Heraklion, Greece</div> </div> <div class="affiliation"> <div class="affiliation-item"><sup>*</sup></div> <div class="affiliation-name ">Authors to whom correspondence should be addressed. </div> </div> </div> </div> <div class="bib-identity" style="margin-bottom: 10px;"> <em>Cancers</em> <b>2021</b>, <em>13</em>(1), 43; <a href="https://doi.org/10.3390/cancers13010043">https://doi.org/10.3390/cancers13010043</a> </div> <div class="pubhistory" style="font-weight: bold; padding-bottom: 10px;"> <span style="display: inline-block">Submission received: 26 November 2020</span> / <span style="display: inline-block">Revised: 16 December 2020</span> / <span style="display: inline-block">Accepted: 22 December 2020</span> / <span style="display: inline-block">Published: 25 December 2020</span> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Special Issue <a href=" /journal/cancers/special_issues/Breakthroughs_Cancer_Related_Immunotherapy ">Breakthroughs in Cancer-Related Immunotherapy</a>)<br/> </div> <div class="highlight-box1"> <div class="download"> <a class="button button--color-inversed button--drop-down" data-dropdown="drop-download-468413" aria-controls="drop-supplementary-468413" aria-expanded="false"> Download <i class="material-icons">keyboard_arrow_down</i> </a> <div id="drop-download-468413" class="f-dropdown label__btn__dropdown label__btn__dropdown--button" data-dropdown-content aria-hidden="true" tabindex="-1"> <a class="UD_ArticlePDF" href="/2072-6694/13/1/43/pdf?version=1608994987" data-name="Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer" data-journal="cancers">Download PDF</a> <br/> <a id="js-pdf-with-cover-access-captcha" href="#" data-target="/2072-6694/13/1/43/pdf-with-cover" class="accessCaptcha">Download PDF with Cover</a> <br/> <a id="js-xml-access-captcha" href="#" data-target="/2072-6694/13/1/43/xml" class="accessCaptcha">Download XML</a> <br/> <a href="/2072-6694/13/1/43/epub" id="epub_link">Download Epub</a> <br/> </div> <div class="js-browse-figures" style="display: inline-block;"> <a href="#" class="button button--color-inversed margin-bottom-10 openpopupgallery UI_BrowseArticleFigures" data-target='article-popup' data-counterslink = "https://www.mdpi.com/2072-6694/13/1/43/browse" >Browse Figure</a> </div> <div id="article-popup" class="popupgallery" style="display: inline; line-height: 200%"> <a href="https://pub.mdpi-res.com/cancers/cancers-13-00043/article_deploy/html/images/cancers-13-00043-ag.png?1608995055" title=" <strong>Graphical abstract</strong><br/> "> </a> </div> <a class="button button--color-inversed" href="/2072-6694/13/1/43/notes">Versions Notes</a> </div> </div> <div class="responsive-moving-container small hidden" data-id="article-counters" style="margin-top: 15px;"></div> <div class="html-dynamic"> <section> <div class="art-abstract art-abstract-new in-tab hypothesis_container"> <p> <div><section class="html-abstract" id="html-abstract"> <h2 id="html-abstract-title">Abstract</h2><b>:</b> <section id="SimpleSummary" type=""><h2 data-nested="1"> Simple Summary</h2><div class="html-p">Immunotherapy and immune checkpoint inhibitors have become the breakthrough treatment with extended responses and survival rates in various neoplasms. They use the immune system to defeat cancer, while gut microbiota seems to play a significant role in that attempt. To date, colorectal cancer patients have gained little benefit from immunotherapy. Only mismatch repair-deficient/microsatellite-unstable tumors seem to respond positively to immunotherapy. However, gut microbiota could be the key to expanding the use of immunotherapy to a greater range of colorectal cancer patients. In the current review study, the authors aimed to present and analyze the mechanisms of action and resistance of immunotherapy and the types of immune checkpoint inhibitors (ICIs) as well as their correlation to gut microbiota. A special reference will be made in the association of immunotherapy and gut microbiota in the colorectal cancer setting.</div></section><section id="Abstract" type=""><h2 data-nested="1"> Abstract</h2><div class="html-p">Over the last few years, immunotherapy has been considered as a key player in the treatment of solid tumors. Immune checkpoint inhibitors (ICIs) have become the breakthrough treatment, with prolonged responses and improved survival results. ICIs use the immune system to defeat cancer by breaking the axes that allow tumors to escape immune surveillance. Innate and adaptive immunity are involved in mechanisms against tumor growth. The gut microbiome and its role in such mechanisms is a relatively new study field. The presence of a high microbial variation in the gut seems to be remarkably important for the efficacy of immunotherapy, interfering with innate immunity. Metabolic and immunity pathways are related with specific gut microbiota composition. Various studies have explored the composition of gut microbiota in correlation with the effectiveness of immunotherapy. Colorectal cancer (CRC) patients have gained little benefit from immunotherapy until now. Only mismatch repair-deficient/microsatellite-unstable tumors seem to respond positively to immunotherapy. However, gut microbiota could be the key to expanding the use of immunotherapy to a greater range of CRC patients.</div></section> </section> <div id="html-keywords"> <div class="html-gwd-group"><div id="html-keywords-title">Keywords: </div><a href="/search?q=immunotherapy">immunotherapy</a>; <a href="/search?q=immune+checkpoint+inhibitors">immune checkpoint inhibitors</a>; <a href="/search?q=gut+microbiota">gut microbiota</a>; <a href="/search?q=colorectal+cancer">colorectal cancer</a></div> <div> </div> </div> </div> </p> </div> <div class="row"> <div class="columns large-12 text-center"> <div class="abstract-image-preview open js-browse-figures"> <a href="#" class="openpopupgallery" data-target='article-popup-ga'> <img src="https://pub.mdpi-res.com/cancers/cancers-13-00043/article_deploy/html/images/cancers-13-00043-ag-550.jpg?1608995055" style="max-width: 100%; max-height: 280px; padding: 10px;"> </a> <div id="article-popup-ga" class="popupgallery" style="display: inline; line-height: 200%"> <a href="https://pub.mdpi-res.com/cancers/cancers-13-00043/article_deploy/html/images/cancers-13-00043-ag.png?1608995055" title="<strong>Graphical Abstract</strong>"></a> </div> <div>Graphical Abstract</div> </div> </div> </div> </section> </div> <div class="hypothesis_container"> <ul class="menu html-nav" data-prev-node="#html-quick-links-title"> </ul> <div class="html-body"> <section id='sec1-cancers-13-00043' type='intro'><h2 data-nested='1'> 1. Introduction</h2><div class='html-p'>There is no doubt that in recent years, a breakthrough has been achieved by introducing immunotherapy as a treatment option for solid tumors. In the past, cytotoxic agents were the main choice for cancer therapy. It was not earlier than 1980 that W. Colley demonstrated that the inoculation of <span class='html-italic'>Streptococcus pyogenes</span> bacteria in sarcoma patients led to cancer remission. This proof-of-concept study demonstrated that the immune system and its modification could be a potential tool against cancer [<a href="#B1-cancers-13-00043" class="html-bibr">1</a>]. The immune system uses two major pathways to defeat an intruder. First, immune cells recognize the pathogen and release of a number of different cytokines, and activation of complement and phagocytosis follow. Then, the adaptive immune system is activated, using B and T lymphocytes for the elimination of the pathogen [<a href="#B2-cancers-13-00043" class="html-bibr">2</a>]. The understanding of such mechanisms and their correlation with cancer elimination has led to many innovations and new treatment options, like immune checkpoint inhibitors (ICIs).</div><div class='html-p'>The human body is colonized by more than 100 trillion microbes that include about 4930 bacterial, eukaryotic and archaeal species, most of which are in the gut. Gut microbiota colonization starts at the time of birth and is remodeled according to diet, way of living, diseases, aging, drug consumption and other environmental factors. The gut of a healthy individual is mainly composed of microbes of <span class='html-italic'>Firmicutes</span> and <span class='html-italic'>Bacteroidetes</span> phyla, whereas <span class='html-italic'>Cyanobacteria</span>, <span class='html-italic'>Proteobacteria</span>, <span class='html-italic'>Actinobacteria</span>, <span class='html-italic'>Fusobacteria</span> and <span class='html-italic'>Verrucomicrobia</span> phyla appear in a minor proportion [<a href="#B3-cancers-13-00043" class="html-bibr">3</a>], which interact with the host directly or through their products, thus regulating homeostasis, inflammation, metabolism and immunity [<a href="#B4-cancers-13-00043" class="html-bibr">4</a>,<a href="#B5-cancers-13-00043" class="html-bibr">5</a>]. Dysbiosis and microbial translocation have been associated with many health disorders, including inflammations, autoimmune disorders and precancerous or cancerous lesions [<a href="#B6-cancers-13-00043" class="html-bibr">6</a>]. It has already been demonstrated that gut microbiota, as an immunomodulator and a modulator of metabolism, could affect the efficacy of immunotherapy in cancer patients [<a href="#B7-cancers-13-00043" class="html-bibr">7</a>,<a href="#B8-cancers-13-00043" class="html-bibr">8</a>,<a href="#B9-cancers-13-00043" class="html-bibr">9</a>,<a href="#B10-cancers-13-00043" class="html-bibr">10</a>,<a href="#B11-cancers-13-00043" class="html-bibr">11</a>,<a href="#B12-cancers-13-00043" class="html-bibr">12</a>,<a href="#B13-cancers-13-00043" class="html-bibr">13</a>,<a href="#B14-cancers-13-00043" class="html-bibr">14</a>,<a href="#B15-cancers-13-00043" class="html-bibr">15</a>,<a href="#B16-cancers-13-00043" class="html-bibr">16</a>,<a href="#B17-cancers-13-00043" class="html-bibr">17</a>].</div><div class='html-p'>Colorectal cancer (CRC) is the third most common cancer worldwide, and in the USA alone, the disease is estimated to cost the medical care system <span>$</span>17 billion in 2020 [<a href="#B18-cancers-13-00043" class="html-bibr">18</a>]. Although significant improvements have been made towards the cure of CRC, immunotherapy has a minor role. To date, only patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSH) tumors seem to benefit from immunotherapy, thus leading to FDA approval for ICIs only for dMMR/MSH CRC patients [<a href="#B19-cancers-13-00043" class="html-bibr">19</a>,<a href="#B20-cancers-13-00043" class="html-bibr">20</a>]. However, only about 15% of all CRCs are dMMR/MSH [<a href="#B21-cancers-13-00043" class="html-bibr">21</a>,<a href="#B22-cancers-13-00043" class="html-bibr">22</a>]. Under these circumstances, new ways are under evaluation to maximize the use and efficacy of immunotherapy in CRC patients. Gut microbiota seems to have a key role in this procedure, and extensive research has been done about this hypothesis.</div><div class='html-p'>In this review study, we aimed to present and analyze the mechanisms of action and resistance of immunotherapy and the types of ICIs, as well as their correlation to gut microbiota. A special reference will be made in the association of immunotherapy and gut microbiota in the CRC setting.</div></section><section id='sec2-cancers-13-00043' type=''><h2 data-nested='1'> 2. Immunotherapy in Solid Tumors</h2><div class='html-p'>Immunotherapy is a relatively new treatment option and has become a powerful clinical strategy against solid tumors. However, not all tumors react in the same manner (<a href="#cancers-13-00043-t001" class="html-table">Table 1</a>). So far, there are two major ICIs classes: the cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and the programmed death receptor and its ligand 1 (PD-1/PD-L1) inhibitors. CTLA-4 is overexpressed on regulatory T lymphocytes (Tregs) and activated CD4+ and CD8+ T cells, whereas, anti-CTLA-4 antibodies enhance anti-tumor immunity [<a href="#B23-cancers-13-00043" class="html-bibr">23</a>,<a href="#B24-cancers-13-00043" class="html-bibr">24</a>]. PD-L1 is expressed by stromal and tumor cells. PD-L1 binds to its receptor (PD-1) on cytotoxic T-lymphocytes (CTLs). Anti-PD-L1 and anti-PD-1 immunotherapy target this complex and the immunosuppression that is provoked [<a href="#B25-cancers-13-00043" class="html-bibr">25</a>]. The approved ICIs include a. anti-CTLA-4: ipilimumab; b. anti-PD-L1: nivolumab, durvalumab, avelumab; and c. anti-PD-1: atezolizumab and pembrolizumab. ICIs are used for a great number of solid tumors, including melanoma, renal cell cancer, hepatocellular cancer, urothelial carcinoma, head and neck carcinoma, non-small and small cell lung cancer, dMMR/MSH CRC or non-CRC and gastric cancer [<a href="#B24-cancers-13-00043" class="html-bibr">24</a>].</div><div class='html-p'>ICIs’ modes of action include the pattern recognition receptors (PRRs), expressed by macrophages and dendritic cells [<a href="#B27-cancers-13-00043" class="html-bibr">27</a>]. Foreign molecules and endogenous stress signals notify the body of the presence of an invader or damage. Then, immune cells release chemokines and type I interferon, leading to further inflammation and CTLs infiltration. Moreover, dendritic cells present the tumor neo-antigens to CTLs [<a href="#B24-cancers-13-00043" class="html-bibr">24</a>]. Following these mechanisms, ICIs either eliminate the activation of Tregs or provoke dendritic cells to release IL-12, leading to further activation of CTLs, thus fighting tumor cells [<a href="#B25-cancers-13-00043" class="html-bibr">25</a>].</div><div class='html-p'>However, immunotherapy seems to be inefficient against every tumor. The question is how this resistance is achieved. It seems to be a complex phenomenon, and two main mechanisms have been described: The first mechanism includes the tumor microenvironment, which overcomes the immune surveillance using its components [<a href="#B28-cancers-13-00043" class="html-bibr">28</a>]. It consists of various immunosuppressive cells, such as Tregs, which express a high amount of fork-head box P3 (FoxP3) transcription factor, secrete inhibitory cytokines and suppress effector T lymphocytes (Teff) [<a href="#B29-cancers-13-00043" class="html-bibr">29</a>,<a href="#B30-cancers-13-00043" class="html-bibr">30</a>]. B regulatory cells (B-regs) suppress cytotoxic CD4+ and CD8+ Teffs [<a href="#B30-cancers-13-00043" class="html-bibr">30</a>]. Myeloid-derived suppressor cells (MDSCs), by the expression of molecules like CD11b and Gr-1, promote immunosuppression against cancer and cancer invasion [<a href="#B31-cancers-13-00043" class="html-bibr">31</a>]. M1 tumor-associated macrophages (TAMs) seem to be implicated in the tumor immunosurveillance and M2 in tumorigenesis [<a href="#B32-cancers-13-00043" class="html-bibr">32</a>,<a href="#B33-cancers-13-00043" class="html-bibr">33</a>]. Other components of the stroma are the tumor-associated mast cells (TAMCs) which promote angiogenesis, tumorigenesis and immunosuppression by releasing a number of proteolytic enzymes and growth factors [<a href="#B34-cancers-13-00043" class="html-bibr">34</a>]. The second mechanism that affects the efficacy of immunotherapy is autophagy. Autophagy regulates the tumor microenvironment, making metabolic changes, creating hypoxic conditions and producing inflammatory and immunosuppressive components [<a href="#B35-cancers-13-00043" class="html-bibr">35</a>]. Autophagy plays an important role in the antigen presentation on the surface of antigen-presenting cells and as a regulator of the major histocompatibility complex [<a href="#B28-cancers-13-00043" class="html-bibr">28</a>,<a href="#B36-cancers-13-00043" class="html-bibr">36</a>].</div><div class='html-p'>Resistance to immunotherapy could also be triggered by molecular changes, oncogenes, genetic or epigenetic alterations and the number of neo-antigens, which are directly related to tumor mutational burden [<a href="#B28-cancers-13-00043" class="html-bibr">28</a>,<a href="#B37-cancers-13-00043" class="html-bibr">37</a>].</div></section><section id='sec3-cancers-13-00043' type=''><h2 data-nested='1'> 3. Gut Microbiota and Immunotherapy</h2><div class='html-p'>Gut microbiota seems to be another regulator of immunotherapy response. Studies have shown that the diversity and abundance of gut microbiota could determine response to immunotherapy by various pathways [<a href="#B6-cancers-13-00043" class="html-bibr">6</a>,<a href="#B38-cancers-13-00043" class="html-bibr">38</a>,<a href="#B39-cancers-13-00043" class="html-bibr">39</a>]. Gut microbiota produces metabolites and forms biofilms that regulate metabolism, inflammation and immunity [<a href="#B38-cancers-13-00043" class="html-bibr">38</a>]. Over the last few years, the development of technology and algorithms allowed the easier and more effective detection and identification of these microorganisms and the testing of their collective contribution to human health without the need for their isolation and culture. Such technology includes next-generation sequencing of the 16S ribosomal RNA and, more recently, whole-genome shotgun sequencing and metagenomic sequencing [<a href="#B40-cancers-13-00043" class="html-bibr">40</a>].</div><section id='sec3dot1-cancers-13-00043' type=''><h4 class='html-italic' data-nested='2'> 3.1. Interference of Gut Microbiota and Immunity</h4><div class='html-p'>Recent studies have demonstrated that gut microbiota affect not only the efficacy of immunotherapy but also the frequency and intensity of its adverse events [<a href="#B12-cancers-13-00043" class="html-bibr">12</a>,<a href="#B24-cancers-13-00043" class="html-bibr">24</a>]. Toll-like (TLRs) and NOD-like receptors (NLRs) are the two major PRRs that are implicated in immunity [<a href="#B41-cancers-13-00043" class="html-bibr">41</a>,<a href="#B42-cancers-13-00043" class="html-bibr">42</a>]. There are nine TLRs subtypes: TLR1,2 and 4–6 recognize the extracellular bacterial components expressed on the cell surface, whereas TLR3 and 7–9 recognize primarily viral nucleic acids [<a href="#B43-cancers-13-00043" class="html-bibr">43</a>]. TLRs bind to their ligands and are involved in signal transduction through the Toll/interleukin-1 receptor (TIR)-domain containing adapter-inducing interferon-β (TRIF) and myeloid differentiation of primary response protein 88 (MYD88). TLR uses either MYD88 or TRIF to transfer the signal, usually by creating heterodimers with other TLRs or complexes with specific adapters. All these steps lead to the activation of nuclear factor-kappa B (NF-κΒ) pathway and the inflammation response [<a href="#B42-cancers-13-00043" class="html-bibr">42</a>,<a href="#B44-cancers-13-00043" class="html-bibr">44</a>,<a href="#B45-cancers-13-00043" class="html-bibr">45</a>]. Deletion of MYD88 signal in the epithelium leads to a numerical increase of mucus-associated microorganisms and their translocation to mesenteric lymph nodes [<a href="#B46-cancers-13-00043" class="html-bibr">46</a>], which is correlated with the development and progression of some cancer types, such as CRC, and their clinical outcome [<a href="#B6-cancers-13-00043" class="html-bibr">6</a>].</div><div class='html-p'>NLRs are a big family of receptors that includes: nucleotide-binding oligomerization domain-1 (NODs), NACHT-, Leucine-rich repeat- and pyrin- domain-containing proteins, Interleukin 1β converting enzyme-protease activating factor, neuronal apoptosis inhibitor factors and class II major histocompatibility complex transactivator [<a href="#B47-cancers-13-00043" class="html-bibr">47</a>]. Each NLR has a unique ligand, recognizing specific microbial components or products and participates in a different manner to the action of innate immunity. For example, <span class='html-italic'>Listeria monocytogenes</span> toxin is the activator of NLR6. NLR6 combines with the adapter apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain, forming inflammasomes in the cytoplasm and leading to the recruitment of caspase-1 and the release of IL-1β, thus shutting down inflammatory response [<a href="#B48-cancers-13-00043" class="html-bibr">48</a>,<a href="#B49-cancers-13-00043" class="html-bibr">49</a>]. All mechanisms that include NLRs seem to play a critical role in the activation of the immune system in the intestinal epithelium, tumor monitoring and immunosurveillance [<a href="#B50-cancers-13-00043" class="html-bibr">50</a>].</div><div class='html-p'>Concerning adaptive immunity, pathogen-associated molecular patterns activate the antigen-presenting cells (APCs), which migrate to mesenteric lymph nodes, where naïve T lymphocytes mature into CD4+ T cells. These cells are differentiated into T helper (Th) cells and Tregs [<a href="#B42-cancers-13-00043" class="html-bibr">42</a>,<a href="#B51-cancers-13-00043" class="html-bibr">51</a>]. These two subtypes are crucial for maintaining a symbiotic balance between the immune system and microbiota, affecting tumor growth and immunosurveillance. Th cells act as regulators by selecting a specific immunoglobin A (IgA) plasma cell bank, expressing PD-1, which binds to PD-L1 on the surface of B cells [<a href="#B52-cancers-13-00043" class="html-bibr">52</a>,<a href="#B53-cancers-13-00043" class="html-bibr">53</a>]. PD-1-deficient mice produce IgAs not capable to properly bind bacteria, and bacterial diversity is disturbed in companion with antibodies required to maintain a mucosal barrier, thus leading to dysbiosis [<a href="#B54-cancers-13-00043" class="html-bibr">54</a>]. Th17 cells play an important role in tumorigenesis through the secretion of IL-17f. There are conflicting data on different cancer types and the role of IL-17f. For instance, in non-small cell lung cancer, IL-17f increases the invasion by promoting angiogenetic chemokines. On the contrary, in CRC, IL-17f suspends angiogenesis through the reduction of vascular endothelial growth factor [<a href="#B55-cancers-13-00043" class="html-bibr">55</a>,<a href="#B56-cancers-13-00043" class="html-bibr">56</a>].</div><div class='html-p'>Tregs express PD-1 and PD-L1 and are in abundance in the lamina propria of the colon. The PD-1/PD-L1 axis also seems to be one of the inhibitors of CD4+ and CD8+ T lymphocytes response, using specific cytokines like transforming growth factor (TGF)-β and IL-10 [<a href="#B42-cancers-13-00043" class="html-bibr">42</a>,<a href="#B57-cancers-13-00043" class="html-bibr">57</a>,<a href="#B58-cancers-13-00043" class="html-bibr">58</a>]. Not only microorganisms, but also their fractions and metabolites, can alter the immune response and interfere with Tregs regulation. These metabolites, such as short-chain fatty acids, activate pathways that can induce the release of IL-10 [<a href="#B59-cancers-13-00043" class="html-bibr">59</a>], increasing the response of T cells to TGF-β1 by regulating the TGF receptor expression [<a href="#B60-cancers-13-00043" class="html-bibr">60</a>]. TGF-β, in parallel, increases the expression of Foxp3 in CD25 T cells, converting them to CD4+ CD25+ induced regulatory T cells (iTregs) [<a href="#B57-cancers-13-00043" class="html-bibr">57</a>], thus leading to further immunosuppression. Other metabolites that could act as immunomodulators through the regulation of Tregs are the symbiotic factor polysaccharide A and butyrate. The symbiotic factor polysaccharide A is produced by <span class='html-italic'>Bacteroides fragilis</span>, leading to increased expression of Foxp3, IL-10 and TGF-β through the motivation of TLR2 on CD4+ cells. Butyrate increases Tregs through activation of Foxp3 [<a href="#B42-cancers-13-00043" class="html-bibr">42</a>]. Dysbiosis leads to the change of quantity and ratio of metabolites, thus leading to different immune reactions. It has been demonstrated that an increase in <span class='html-italic'>Clostridium</span> spp. and <span class='html-italic'>B. fragilis</span> led to an increase in iTregs in the gut [<a href="#B39-cancers-13-00043" class="html-bibr">39</a>]. iTregs, through metabolic and proliferating pathways, play an important role in PD-1/PD-L1 axis and in the efficacy of anti-PD-1/PD-L1 immunotherapy; however, the mechanism remains to be explored [<a href="#B61-cancers-13-00043" class="html-bibr">61</a>,<a href="#B62-cancers-13-00043" class="html-bibr">62</a>].</div></section><section id='sec3dot2-cancers-13-00043' type=''><h4 class='html-italic' data-nested='2'> 3.2. Correlation of Gut Microbiota and ICIs Efficacy: The Proofs</h4><div class='html-p'>Many studies have concluded that gut microbiota can interfere with the efficacy of immunotherapy [<a href="#B7-cancers-13-00043" class="html-bibr">7</a>,<a href="#B8-cancers-13-00043" class="html-bibr">8</a>,<a href="#B9-cancers-13-00043" class="html-bibr">9</a>,<a href="#B10-cancers-13-00043" class="html-bibr">10</a>,<a href="#B11-cancers-13-00043" class="html-bibr">11</a>]. The breakthrough of this scenario came by Sivan et al. [<a href="#B7-cancers-13-00043" class="html-bibr">7</a>], who enrolled in their study Black-6 mice from different vendors, Taconic Biosciences (TAC) and Jackson Laboratories (JAX), aiming to study the role of microbiota in melanoma development and progression. TAC mice were shown to suffer from more severe melanoma than JAX mice. When TAC and JAX were housed together before melanoma cell implantation, such differences disappeared. Using fecal suspension of the two mice as feeding, it was demonstrated that JAX gut microbiota provided an anti-tumor effect. Combining fecal suspension of JAX mice with anti-PD-L1 immunotherapy led to an improvement of ICI efficacy by increasing T cell responses and decreasing tumor growth, while the shorter tumor growth was correlated with the presence of <span class='html-italic'>Bifidobacterium</span> spp. [<a href="#B7-cancers-13-00043" class="html-bibr">7</a>]. Derosa et al. collected stool samples from both responders and non-responders to immunotherapy who experienced renal cell carcinoma (RCC), non-small cell lung cancer or urothelial carcinoma. The authors performed fecal microbial transplantation in germ-free or antibiotic-treated mice. Mice transplanted with fecal material from responders presented more immuno-efficacy than the non-responders’, leading to tumor reduction. As was demonstrated, the presence of <span class='html-italic'>Akkermansia muciniphila</span> in the gut contributed to anti-PD1 efficacy [<a href="#B8-cancers-13-00043" class="html-bibr">8</a>,<a href="#B63-cancers-13-00043" class="html-bibr">63</a>].</div><div class='html-p'>Different studies, focused mainly on melanoma, aimed to examine the differences in gut microbiota between responders and non-responders [<a href="#B9-cancers-13-00043" class="html-bibr">9</a>,<a href="#B10-cancers-13-00043" class="html-bibr">10</a>,<a href="#B11-cancers-13-00043" class="html-bibr">11</a>,<a href="#B12-cancers-13-00043" class="html-bibr">12</a>]. Frankel et al. used anti-PD-1 and anti-CTLA-4 as a standalone or in combination to treat melanoma patients. It was shown that responders’ gut microbiota was mainly composed of <span class='html-italic'>Faecalibacterium prausnitzii</span>, <span class='html-italic'>Bacteroides thetaiotamicron</span>, <span class='html-italic'>Holdemania filiformis</span> and <span class='html-italic'>Bacteroides caccae</span> [<a href="#B9-cancers-13-00043" class="html-bibr">9</a>]. Gopalakrishnan et al. studied the response and gut microbiota, as well as immunocytes, in melanoma patients under anti-PD-1 treatment. The responders’ (69.8%) gut microbiota was mainly composed of <span class='html-italic'>F. prausnitzii</span>, <span class='html-italic'>Ruminococcus bromii</span>, <span class='html-italic'>Porphyromonas pasteri</span>, <span class='html-italic'>Clostridium hungati</span> and <span class='html-italic'>Phascolarctobacterium faecium</span>, whereas gut microbiota of the non-responders was mainly composed of <span class='html-italic'>B. thetaiotaomicron</span>, <span class='html-italic'>Escherichia coli</span> and <span class='html-italic'>Anaerotruncus colihomininis</span> [<a href="#B10-cancers-13-00043" class="html-bibr">10</a>]. Immunohistochemistry on tumor specimens and flow cytometry blood samples revealed decreased Tregs and MDSCs with increase in CD8+ T cells and CD68+ HLA-Dr+ CD163+ myeloid dendritic cells [<a href="#B10-cancers-13-00043" class="html-bibr">10</a>]. Moreover, Chaput et al. demonstrated correlations of anti-CTLA-4 efficacy and adverse events with gut microbiota in melanoma patients. <span class='html-italic'>F. prausnitzii</span> L2-6, <span class='html-italic'>Gemmiger formicilitis</span> ATCC27749, butyrate- producing bacteria SS2-1, <span class='html-italic'>Ruminococcus</span> spp., <span class='html-italic'>Lachnospiraceae</span> spp., <span class='html-italic'>Clostridium</span> XIVa and <span class='html-italic'>Blautia</span> spp. correlated with better tumor reduction but increased events of ICI-associated colitis. On the contrary, <span class='html-italic'>Bacteroides</span> spp. were mainly correlated with worse tumor remission and fewer events of colitis [<a href="#B12-cancers-13-00043" class="html-bibr">12</a>]. This is in agreement with Dublin et al., who demonstrated ICI-associated colitis in 29.4% of melanoma patients under anti-CTLA-4, and their gut microbiota was mainly composed of microorganisms belonging to the phylum of <span class='html-italic'>Bacteroidetes</span>, families of <span class='html-italic'>Bacteroidaceae</span>, <span class='html-italic'>Rikenellaceae</span> and <span class='html-italic'>Barnesiellaceae</span> [<a href="#B11-cancers-13-00043" class="html-bibr">11</a>]. A recently published meta-analysis of four shotgun metagenomic studies in metastatic melanoma patients receiving immunotherapy showed differences of microbial composition in the gut of responders and non-responders and examined the predictive value of this composition [<a href="#B64-cancers-13-00043" class="html-bibr">64</a>]. The gut of responders was enriched with unknown <span class='html-italic'>Ruminococcaceae</span> and <span class='html-italic'>Faecalibacterium</span> spp., <span class='html-italic'>Ruminococcus bicirculans</span> and <span class='html-italic'>Barnesiella intestinihomini</span>, whereas non-responders were mainly colonized by <span class='html-italic'>B. thetaiotaomicron</span>, <span class='html-italic'>Adlercreutzia equolifaciens</span>, <span class='html-italic'>Bifidobacterium dentium</span> and unknown <span class='html-italic'>Mogibacterium</span> spp. [<a href="#B64-cancers-13-00043" class="html-bibr">64</a>]. Moreover, comparison of gut microbial networks of responders and non-responders revealed that responders’ networks had an abundance of <span class='html-italic'>Mogibacterium</span>, <span class='html-italic'>Anaerococcus</span> and <span class='html-italic'>Eggerthella</span> spp. while non-responders had an abundance of <span class='html-italic'>Subdoligranulum</span>, <span class='html-italic'>Lachnoclostridium</span>, <span class='html-italic'>Eggerthella</span> and <span class='html-italic'>Streptococcus</span> spp. The abundance of unknown <span class='html-italic'>Faecalibacterium</span> sp. and of aerobic respiration provided predictive value for the efficacy of immunotherapy [<a href="#B64-cancers-13-00043" class="html-bibr">64</a>].</div><div class='html-p'>Regarding all the above-mentioned, gut microbiota not only promotes the efficacy of immunotherapy and regulates the emergence of adverse events, but also helps immunotherapy to overcome the tumor’s resistance.</div><div class='html-p'>Some microbial species can be synergic to ICIs, while others not. <span class='html-italic'>Bifidobacteria</span> spp. promote immune response by inducing transcription of dendritic cell genes, leading to their maturation. They can downregulate the threshold of their activation, thus needing less antigens to initiate T cells [<a href="#B7-cancers-13-00043" class="html-bibr">7</a>,<a href="#B42-cancers-13-00043" class="html-bibr">42</a>]. <span class='html-italic'>B. fragilis</span> is the activator of Th1 cells, leading them to react with antigens promoting the efficacy of anti-CTLA-4. Moreover, IL-12 is produced as a result of the mobilization of CD11b+ DC to lamina propria by <span class='html-italic'>B. fragilis</span>, leading to better anti-tumor response [<a href="#B65-cancers-13-00043" class="html-bibr">65</a>,<a href="#B66-cancers-13-00043" class="html-bibr">66</a>,<a href="#B67-cancers-13-00043" class="html-bibr">67</a>]. <span class='html-italic'>A. muciniphila</span> and <span class='html-italic'>Enterococcus hirae</span> help to increase central memory tumor cells in the tumor. Such cells have specific chemokine receptors, and the axis in which they are involved leads to better survival rates in some advanced cancers [<a href="#B63-cancers-13-00043" class="html-bibr">63</a>]. <span class='html-italic'>Faecalibacterium</span> spp. promotes dendritic and other APCs in order to achieve CD4+ or CD8+ proliferation and also promotes the production of Tregs, resulting in better anti-CTLA-4 efficacy [<a href="#B26-cancers-13-00043" class="html-bibr">26</a>,<a href="#B68-cancers-13-00043" class="html-bibr">68</a>]. On the contrary, <span class='html-italic'>Bacteroides</span> spp. upregulate Tregs and MDSCs, leading to blockage of anti-PD-1 immunotherapy and to an inflammatory response through the TLR-NF pathway that degrades the efficacy of anti-CTLA-4 [<a href="#B69-cancers-13-00043" class="html-bibr">69</a>,<a href="#B70-cancers-13-00043" class="html-bibr">70</a>].</div></section><section id='sec3dot3-cancers-13-00043' type=''><h4 class='html-italic' data-nested='2'> 3.3. Gut Microbiota Modulators and Their Impact on ICIs Efficacy</h4><div class='html-p'>The question that arises is how gut microbiota could be remodeled to obtain the maximum benefit. Apart from fecal microbial transplantation, other exogenous factors are involved in the composition of gut microbiota. The mode of birth delivery and breast or formula feeding during the early life of the infant plays an important role in the jumpstart of gut microbiota. Generally, diet affects gut microbiota. The metabolites produced by the degradation of the food in the gut from different microorganisms play a crucial role in the modulation of different human body’s operations, like immunity [<a href="#B71-cancers-13-00043" class="html-bibr">71</a>]. A diet rich in fibers and grains is preferred over one with red meat. Consumption of prebiotics, probiotics or synbiotics can strengthen the microbial function of the gut [<a href="#B72-cancers-13-00043" class="html-bibr">72</a>]. Drugs, such as antibiotics or antacids, are also involved in the factors that modulate gut microbiota. Antibiotics have a negative impact on the beneficial bacteria of the gut, decreasing the efficacy of the immunotherapy antitumor treatment [<a href="#B73-cancers-13-00043" class="html-bibr">73</a>]. It has been shown that the efficacy of anti-CTLA-4 is decreased in germ-free and specific-pathogen-free mice that received antibiotics in advance [<a href="#B67-cancers-13-00043" class="html-bibr">67</a>]. When mice were fed with <span class='html-italic'>B. fragilis</span> combined with <span class='html-italic'>Burkholderia cepacia</span> or <span class='html-italic'>B. thetaiotaomicron</span>, immunotherapy efficacy against tumors was restored through Th1 mediated response and activation of dendritic cells in the tumor [<a href="#B67-cancers-13-00043" class="html-bibr">67</a>]. Antibiotics are strongly negatively correlated with overall survival in melanoma, bladder cancer, non-small cell lung cancer and renal cell carcinoma when treated with ICIs [<a href="#B74-cancers-13-00043" class="html-bibr">74</a>]. Moreover, the use of corticosteroids has been significantly negatively correlated with ICI efficacy, with an impact on overall survival in melanoma, non-small cell lung cancer and other carcinomas, although there are no adequate prospective data [<a href="#B75-cancers-13-00043" class="html-bibr">75</a>].</div><div class='html-p'>Additionally, proton-pump inhibitors and metformin have led to the change of gut microbial diversity and taxonomical changes. These changes could have positive or negative effects in tumorigenesis or treatment efficacy [<a href="#B76-cancers-13-00043" class="html-bibr">76</a>,<a href="#B77-cancers-13-00043" class="html-bibr">77</a>]. Proton-pump inhibitors have been related to worse overall survival and progression free survival in patients with non-small cell lung cancer and urothelial cancer following anti-PD-L1 treatment [<a href="#B78-cancers-13-00043" class="html-bibr">78</a>,<a href="#B79-cancers-13-00043" class="html-bibr">79</a>]. Case-control and cohort studies present conflicting data about the relation of proton-pump inhibitors use and the risk of CRC [<a href="#B80-cancers-13-00043" class="html-bibr">80</a>,<a href="#B81-cancers-13-00043" class="html-bibr">81</a>]. However, Lei et al., reported that the extended use of proton-pump inhibitors has been correlated with high risk of CRC [<a href="#B82-cancers-13-00043" class="html-bibr">82</a>]. It has been demonstrated that dysbiosis is correlated with decreased ICIs efficacy and increased risk of tumorigenesis [<a href="#B76-cancers-13-00043" class="html-bibr">76</a>,<a href="#B83-cancers-13-00043" class="html-bibr">83</a>]. The main mechanism is actually the remodeling of microbial diversity, with oral microorganisms, such as <span class='html-italic'>F. nucleatum</span>, being in high abundance. Proton-pump inhibitors might also lead to bacterial overgrowth in the gut, overproduction of their metabolites and formation of precancerous lesions due to chronic inflammation, as a result of microscopic colitis [<a href="#B76-cancers-13-00043" class="html-bibr">76</a>,<a href="#B83-cancers-13-00043" class="html-bibr">83</a>,<a href="#B84-cancers-13-00043" class="html-bibr">84</a>,<a href="#B85-cancers-13-00043" class="html-bibr">85</a>]. On the other hand, metformin, a drug used for the treatment of type 2 diabetes mellitus, targets hepatocytes and the decrease of gluconeogenesis [<a href="#B86-cancers-13-00043" class="html-bibr">86</a>]. Studies have concluded that its action can be mediated by the modulation of gut microbiota [<a href="#B86-cancers-13-00043" class="html-bibr">86</a>,<a href="#B87-cancers-13-00043" class="html-bibr">87</a>,<a href="#B88-cancers-13-00043" class="html-bibr">88</a>]. Sun et al., demonstrated that the use of metformin led to the reduction of <span class='html-italic'>B. fragilis</span> in the gut [<a href="#B86-cancers-13-00043" class="html-bibr">86</a>]. Metformin in mice models led to the enrichment of <span class='html-italic'>Verrucomicrobiaceae</span> and <span class='html-italic'>Prevotellaceae</span> and depletion of <span class='html-italic'>Lachnospiraceae</span> and <span class='html-italic'>Rhodobacteraceae</span> [<a href="#B87-cancers-13-00043" class="html-bibr">87</a>]. It has also been shown that in a group of patients with type 2 diabetes mellitus, metformin led to the enrichment of gut microbiota with <span class='html-italic'>Esherichia</span> and a decrease in <span class='html-italic'>Intestinibacter</span> spp. [<a href="#B89-cancers-13-00043" class="html-bibr">89</a>]. Metformin seems to enhance efficacy of immunotherapy and plays a protective role against tumorigenesis, especially in the case of CRC. Interventions in gut microbiota composition seem to be one of the main mechanisms contributing to these actions [<a href="#B77-cancers-13-00043" class="html-bibr">77</a>,<a href="#B90-cancers-13-00043" class="html-bibr">90</a>,<a href="#B91-cancers-13-00043" class="html-bibr">91</a>]. Metformin enriches gut microbiota with <span class='html-italic'>A. muciniphilla</span>, a microorganism that has been correlated with better anti-PD-1 efficacy. In addition, metformin increases the short-chain fatty acids-producing bacteria, which could induce Tregs proliferation leading to anti-CTLA 4 sensitivity [<a href="#B77-cancers-13-00043" class="html-bibr">77</a>]. Apart from its ability to improve efficacy of immunotherapy, metformin is an antitumor protector, as previously demonstrated [<a href="#B90-cancers-13-00043" class="html-bibr">90</a>,<a href="#B92-cancers-13-00043" class="html-bibr">92</a>]. Higurashi et al. mention that metformin administration as chemoprevention post polypectomy in non-diabetic patients led to a statistically significantly lower incidence of metachronous adenomas or polyps [<a href="#B92-cancers-13-00043" class="html-bibr">92</a>]. Huang et al. showed that metformin can change gut microbiota composition by affecting <span class='html-italic'>Bacteroides</span>, <span class='html-italic'>Streptococcus</span>, <span class='html-italic'>Achromobacter</span>, <span class='html-italic'>Alistipes</span> and <span class='html-italic'>Fusobacterium</span> spp. Especially for <span class='html-italic'>F. nucleatum</span>, which is strongly related to CRC development, metformin relieved the symptoms in APC<sup>min/+</sup> mice [<a href="#B90-cancers-13-00043" class="html-bibr">90</a>,<a href="#B93-cancers-13-00043" class="html-bibr">93</a>].</div></section></section><section id='sec4-cancers-13-00043' type=''><h2 data-nested='1'> 4. Immunotherapy and Microbiota in CRC</h2><div class='html-p'>CRC is one of the leading causes of death due to cancer worldwide. It is a matter of public health, as it financially burdens different health systems, and its early diagnosis by a colonoscopy or a stool-based test for the detection of hemoglobin can have a great impact on the survival of patients [<a href="#B94-cancers-13-00043" class="html-bibr">94</a>]. Immunotherapy is a novelty for the last few years for the treatment of different types of cancer. However, in the case of CRC, only a subgroup of CRCs can benefit from immunotherapy. In particular, only anti-PD-1 has approval for its use in metastatic dMMR/MSH CRC [<a href="#B20-cancers-13-00043" class="html-bibr">20</a>,<a href="#B95-cancers-13-00043" class="html-bibr">95</a>]. It is challenging to understand how to improve the efficacy of immunotherapy not only in dMMR/MSH CRC but also in MMR-proficient CRC. The rationale behind the use of immunotherapy in CRC was that especially dMMR/MSH tumors have a higher amount of neo-antigens capable to enforce immunity against tumors [<a href="#B14-cancers-13-00043" class="html-bibr">14</a>].</div><div class='html-p'>Gut microbiota seems to play a crucial role in tumorigenesis but also in immunomodulation and immunosensitivity of CRC (<a href="#cancers-13-00043-t002" class="html-table">Table 2</a>). Microbial dysbiosis and translocation have been correlated with CRC development and progression [<a href="#B6-cancers-13-00043" class="html-bibr">6</a>,<a href="#B96-cancers-13-00043" class="html-bibr">96</a>]. Intracellular signaling pathways, like unfolded protein response, when activated, fail to reduce the stress of the endoplasmic reticulum, leading to homeostasis disturbances. The activating transcription factor 6 (ATF6) leads to an increase in endoplasmic reticulum capacity and the destruction of defective proteins. Coleman et al. showed that the activated ATF6 leads to intestinal dysbiosis, activation of the immune system and CRC development [<a href="#B96-cancers-13-00043" class="html-bibr">96</a>]. It has been demonstrated that the interaction between healthy cells and microbiota or its products could lead to tumorigenesis. <span class='html-italic'>Fusobacterium</span> spp. are a characteristic example of such a hypothesis. Mice models of sporadic CRC of Apc<sup>Min/+</sup> were inoculated with <span class='html-italic'>Fusobacterium nucleatum</span> developed more colon tumors than those inoculated with <span class='html-italic'>Streptococcus</span> spp. and demonstrated a proinflammatory phenotype without colitis exacerbation [<a href="#B93-cancers-13-00043" class="html-bibr">93</a>,<a href="#B97-cancers-13-00043" class="html-bibr">97</a>]. Adhesion bacterial proteins FadA and Fap2 seem to be highly involved in tumorigenesis due to <span class='html-italic'>F. nucleatum</span>. Bacterial FadA promotes tumorigenesis through activation of WNT/β-catenin signaling, whereas Fap2 promotes avoidance of the tumor immunosurveillance. Bacterial Fap2 binds to T cell immunoglobin and the immunoreceptor tyrosine-based inhibition motif domain, an inhibitory receptor expressed by natural killer and T cells [<a href="#B98-cancers-13-00043" class="html-bibr">98</a>]. It has been shown that <span class='html-italic'>F. nucleatum</span> abundance in the gut is associated with dMMR CRC [<a href="#B99-cancers-13-00043" class="html-bibr">99</a>]. Lee et al. categorized dMMR CRC tumors into <span class='html-italic'>F. nucleatum</span>-high and <span class='html-italic'>F. nucleatum</span>-low tumors. It was revealed that <span class='html-italic'>F. nucleatum</span>-high tumors are characterized by increased tumor growth and invasion, an immune microenvironment with decreased FoxP3<sup>+</sup> T cells through the tumor and a high proportion of M2-macrophages in the tumor center. These findings correlate the presence of <span class='html-italic'>F. nucleatum</span> with pro-cancerous immune responses in dMMR CRC tumors [<a href="#B100-cancers-13-00043" class="html-bibr">100</a>]. Other microorganisms of the gut microbiota, such as <span class='html-italic'>Bacteroides</span> spp. and <span class='html-italic'>Faecalibacterium</span> sp, are significantly correlated with the abundance of tumor-infiltrating immune cells, which determine, to a significant extent, the immunosurveillance of CRC [<a href="#B13-cancers-13-00043" class="html-bibr">13</a>].</div><div class='html-p'>Butyrate is a product of bacterial metabolism in the gut and is involved both in the antitumor immune response and in homeostasis. According to the Warburg effect, butyrate leads to a reduction in mRNA expression of cell-cycle regulators and to an increase in mRNA expression of proapoptotic gene Fas, thus leading to apoptosis [<a href="#B101-cancers-13-00043" class="html-bibr">101</a>]. However, in dMMR/MSH mice, butyrate leads to hyperproliferation [<a href="#B102-cancers-13-00043" class="html-bibr">102</a>], suspends tumor growth and reserves microbial homeostasis by upregulating TLR4 expression and phosphorylation of MAPKs and NF-κΒ in human colon cancer SW480 cells or mouse colon cancer CT26 cells [<a href="#B103-cancers-13-00043" class="html-bibr">103</a>]. Modulators of gut microbiota could be a target to improve immunotherapy efficacy in CRC. Indoleamine 2, 3-dioxygenase 1 (IDO1) is a key factor for the resistance of host-microbiome homeostasis. IDO-1 expressed by cancer cells and dendritic cells is a starter enzyme for the tryptophan metabolism pathway and suppresses the immune response against the tumor [<a href="#B15-cancers-13-00043" class="html-bibr">15</a>]. IDO-1 interferes in host-microbiome interactions either by the activation of several PRRs, which induces IDO-1 expression, or by bacterial metabolites and their interaction with tryptophan metabolism [<a href="#B15-cancers-13-00043" class="html-bibr">15</a>]. TLR4 and TLR9 are the major representatives of PRRs, whereas butyrate and short-chain fatty acids are the main representatives of microbial products in such a process [<a href="#B15-cancers-13-00043" class="html-bibr">15</a>,<a href="#B104-cancers-13-00043" class="html-bibr">104</a>,<a href="#B105-cancers-13-00043" class="html-bibr">105</a>,<a href="#B106-cancers-13-00043" class="html-bibr">106</a>,<a href="#B107-cancers-13-00043" class="html-bibr">107</a>]. IDO-1 inhibitors, alone or in combination, are under investigation for the treatment of CRC, mostly in the dMMR/MSH setting [<a href="#B14-cancers-13-00043" class="html-bibr">14</a>,<a href="#B15-cancers-13-00043" class="html-bibr">15</a>]. Phan et al. aimed to assess the therapeutic efficacy of attenuated <span class='html-italic'>Salmonella typhimurium</span> delivering a small hairpin RNA plasmid targeting IDO (shIDO-ST). Both in vitro and in vivo studies were performed in CT26 and MC38 murine colon cancer models. It was demonstrated that both IDO protein expression and function were reduced and tumor progression was significantly delayed when epacadostat, a known IDO-1 inhibitor, was used [<a href="#B108-cancers-13-00043" class="html-bibr">108</a>]. In mouse colon cancer models, anti-CTLA-4 ICI in combination with <span class='html-italic'>Lactobacillus acidophilus</span> lysates improved antitumor immune response through the increase of infiltrated T cells in the tumor microenvironment. <span class='html-italic'>L. acidophilus</span> lysates also improved homeostasis in these mice [<a href="#B16-cancers-13-00043" class="html-bibr">16</a>]. Moreover, Xu et al., demonstrated that gut microbiota influences the efficacy of anti-PD-1 in MMR-proficient CRC through the glycerolphospholipid metabolic pathway. The authors aimed to evaluate the effects of gut microbiota in CT26 CRC mice treated with different antibiotics on anti-PD-1 response compared to a control group (treated with sterile drinking water). Mice gut microbiota under different antibiotics was remodeled, changing the metabolome and immunity of these mice, thus affecting anti-PD-1 efficacy [<a href="#B17-cancers-13-00043" class="html-bibr">17</a>].</div><div class='html-p'>Many studies with different regimens are under investigation in order to achieve a wider use of immunotherapy in CRC. These include different ICIs, vaccines, adaptive cell transfer, IDO-1 inhibitors and the carcinoembryonic antigen T cell biphasic antibody [<a href="#B14-cancers-13-00043" class="html-bibr">14</a>]. In mouse models under ICIs, it has already been demonstrated that specific bacterial species are linked to better responses. In CRC, the MC38 cell line has been used in two studies that treated the cells with anti-IL-10 plus CpG oligonucleotides and anti-PD-1 or anti-CTLA-4, respectively. It was demonstrated that <span class='html-italic'>Alistipes shahii</span> and <span class='html-italic'>Ruminococcus</span> spp. played the role of promoters of antitumor response [<a href="#B109-cancers-13-00043" class="html-bibr">109</a>]. Additionally, <span class='html-italic'>Ruthenibacterium lactatiformans</span>, <span class='html-italic'>Eubacterium limosum</span>, <span class='html-italic'>F. ulcerans</span>, <span class='html-italic'>Phascolarctobacterium succinatutens</span>, <span class='html-italic'>B. uniformis</span>, <span class='html-italic'>Bacteroides dorei</span>, <span class='html-italic'>Paraprevotella xylaniphila</span>, <span class='html-italic'>Parabacteroides johnsonii</span>, <span class='html-italic'>P. gordonii</span> and <span class='html-italic'>Alistipes senegalensis</span> were shown to contribute to improving ICIs efficacy [<a href="#B110-cancers-13-00043" class="html-bibr">110</a>].</div></section><section id='sec5-cancers-13-00043' type='conclusions'><h2 data-nested='1'> 5. Conclusions</h2><div class='html-p'>Immunotherapy is a new hallmark of solid tumor treatment. Extensions in survival rates and longer-lasting responses have been achieved in various cancers. Melanoma, non-small cell lung cancer, renal cell and urothelial carcinoma are some of them. The rationale of immunotherapy is to boost the immune system response to tumor growth or to overlap the barriers that were created by the tumor itself or the tumor’s microenvironment. Innate and adaptive immunity are equally involved in the inhibition of tumor growth. Numerous efforts have been made through the years, and different molecules have been used aiming to work in concert with the immune system to defeat cancers. Nowadays, ICIs are the main players in this effort. Anti-PD-1, anti-PD-L1 and anti-CTLA-4 are the main immunotherapy options that aid immune system to overcome checkpoints leading to immune escape. However, some cancer types, like CRC, have little or no benefit from such immunotherapy. For all these reasons, several studies are in progress aiming to contribute to better efficacy of immunotherapy.</div><div class='html-p'>Gut microbiota plays a crucial role in the interplay of tumor and immune system. A number of studies have shown that different bacterial species can increase the efficacy of immunotherapy [<a href="#B7-cancers-13-00043" class="html-bibr">7</a>,<a href="#B24-cancers-13-00043" class="html-bibr">24</a>,<a href="#B63-cancers-13-00043" class="html-bibr">63</a>,<a href="#B67-cancers-13-00043" class="html-bibr">67</a>,<a href="#B109-cancers-13-00043" class="html-bibr">109</a>,<a href="#B111-cancers-13-00043" class="html-bibr">111</a>]. Gut microbiota interferes with the immune system, mainly through innate immunity. Studies are in progress to evaluate how gut microbiota would enhance prognosis and treatment [<a href="#B42-cancers-13-00043" class="html-bibr">42</a>]. Moreover, due to the fact that only dMMR/MSH tumors can benefit from ICIs, new aspects are under investigation for the use of ICIs in MMR-proficient tumors. Therefore, immunotherapy is the new achievement in cancer therapy. The microbiome is the new “human organ” that interferes with all the important functions of the organism. Gut microbiota could be the promoter for a better efficacy of immunotherapy. New aspects to immunotherapy efficacy, even in immunotherapy-resistant cancers, such as MMR-proficient CRC, could be improved by aiming to regulate of the different parts that shape and maintaining the homeostasis of gut microbiota.</div></section> </div> <div class="html-back"> <section class='html-notes'><h2 >Author Contributions</h2><div class='html-p'>All authors have read and agreed to the published version of the manuscript.</div></section><section class='html-notes'><h2 >Funding</h2><div class='html-p'>This research received no external funding.</div></section><section class='html-notes'><h2 >Conflicts of Interest</h2><div class='html-p'>The authors declare no conflict of interest.</div></section><section id='html-references_list'><h2>References</h2><ol class='html-xxx'><li id='B1-cancers-13-00043' class='html-x' data-content='1.'>Decker, W.K.; da Silva, R.F.; Sanabria, M.H.; Angelo, L.S.; Guimaraes, F.; Burt, B.M.; Kheradmand, F.; Paust, S. Cancer Immunotherapy: Historical Perspective of a Clinical Revolution and Emerging Preclinical Animal Models. <span class='html-italic'>Front. Immunol.</span> <b>2017</b>, <span class='html-italic'>8</span>, 829. [<a href="https://scholar.google.com/scholar_lookup?title=Cancer+Immunotherapy:+Historical+Perspective+of+a+Clinical+Revolution+and+Emerging+Preclinical+Animal+Models&author=Decker,+W.K.&author=da+Silva,+R.F.&author=Sanabria,+M.H.&author=Angelo,+L.S.&author=Guimaraes,+F.&author=Burt,+B.M.&author=Kheradmand,+F.&author=Paust,+S.&publication_year=2017&journal=Front.+Immunol.&volume=8&pages=829&doi=10.3389/fimmu.2017.00829" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3389/fimmu.2017.00829" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://www.frontiersin.org/articles/10.3389/fimmu.2017.00829/pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B2-cancers-13-00043' class='html-x' data-content='2.'>Pio, R.; Ajona, D.; Ortiz-Espinosa, S.; Mantovani, A.; Lambris, J.D. Complementing the Cancer-Immunity Cycle. <span class='html-italic'>Front. Immunol.</span> <b>2019</b>, <span class='html-italic'>10</span>, 774. [<a href="https://scholar.google.com/scholar_lookup?title=Complementing+the+Cancer-Immunity+Cycle&author=Pio,+R.&author=Ajona,+D.&author=Ortiz-Espinosa,+S.&author=Mantovani,+A.&author=Lambris,+J.D.&publication_year=2019&journal=Front.+Immunol.&volume=10&pages=774&doi=10.3389/fimmu.2019.00774&pmid=31031765" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3389/fimmu.2019.00774" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/31031765" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://www.frontiersin.org/articles/10.3389/fimmu.2019.00774/pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B3-cancers-13-00043' class='html-x' data-content='3.'>Eckburg, P.B.; Bik, E.M.; Bernstein, C.N.; Purdom, E.; Dethlefsen, L.; Sargent, M.; Gill, S.R.; Nelson, K.E.; Relman, D.A. Diversity of the human intestinal microbial flora. <span class='html-italic'>Science</span> <b>2005</b>, <span class='html-italic'>308</span>, 1635–1638. [<a href="https://scholar.google.com/scholar_lookup?title=Diversity+of+the+human+intestinal+microbial+flora&author=Eckburg,+P.B.&author=Bik,+E.M.&author=Bernstein,+C.N.&author=Purdom,+E.&author=Dethlefsen,+L.&author=Sargent,+M.&author=Gill,+S.R.&author=Nelson,+K.E.&author=Relman,+D.A.&publication_year=2005&journal=Science&volume=308&pages=1635%E2%80%931638&doi=10.1126/science.1110591" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1126/science.1110591" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://europepmc.org/articles/pmc1395357?pdf=render" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B4-cancers-13-00043' class='html-x' data-content='4.'>Rinninella, E.; Raoul, P.; Cintoni, M.; Franceschi, F.; Miggiano, G.A.D.; Gasbarrini, A.; Mele, M.C. What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. <span class='html-italic'>Microorganisms</span> <b>2019</b>, <span class='html-italic'>7</span>, 14. [<a href="https://scholar.google.com/scholar_lookup?title=What+is+the+Healthy+Gut+Microbiota+Composition?+A+Changing+Ecosystem+across+Age,+Environment,+Diet,+and+Diseases&author=Rinninella,+E.&author=Raoul,+P.&author=Cintoni,+M.&author=Franceschi,+F.&author=Miggiano,+G.A.D.&author=Gasbarrini,+A.&author=Mele,+M.C.&publication_year=2019&journal=Microorganisms&volume=7&pages=14&doi=10.3390/microorganisms7010014&pmid=30634578" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3390/microorganisms7010014" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/30634578" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://www.mdpi.com/2076-2607/7/1/14/pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B5-cancers-13-00043' class='html-x' data-content='5.'>Ursell, L.K.; Metcalf, J.L.; Parfrey, L.W.; Knight, R. Defining the human microbiome. <span class='html-italic'>Nutr. Rev.</span> <b>2012</b>, <span class='html-italic'>70</span> (Suppl. 1), S38–S44. [<a href="https://scholar.google.com/scholar_lookup?title=Defining+the+human+microbiome&author=Ursell,+L.K.&author=Metcalf,+J.L.&author=Parfrey,+L.W.&author=Knight,+R.&publication_year=2012&journal=Nutr.+Rev.&volume=70&pages=S38%E2%80%93S44&doi=10.1111/j.1753-4887.2012.00493.x&pmid=22861806" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1111/j.1753-4887.2012.00493.x" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/22861806" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="http://europepmc.org/articles/pmc3426293?pdf=render" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B6-cancers-13-00043' class='html-x' data-content='6.'>Messaritakis, I.; Vogiatzoglou, K.; Tsantaki, K.; Ntretaki, A.; Sfakianaki, M.; Koulouridi, A.; Tsiaoussis, J.; Mavroudis, D.; Souglakos, J. The Prognostic Value of the Detection of Microbial Translocation in the Blood of Colorectal Cancer Patients. <span class='html-italic'>Cancers</span> <b>2020</b>, <span class='html-italic'>12</span>, 1058. [<a href="https://scholar.google.com/scholar_lookup?title=The+Prognostic+Value+of+the+Detection+of+Microbial+Translocation+in+the+Blood+of+Colorectal+Cancer+Patients&author=Messaritakis,+I.&author=Vogiatzoglou,+K.&author=Tsantaki,+K.&author=Ntretaki,+A.&author=Sfakianaki,+M.&author=Koulouridi,+A.&author=Tsiaoussis,+J.&author=Mavroudis,+D.&author=Souglakos,+J.&publication_year=2020&journal=Cancers&volume=12&pages=1058&doi=10.3390/cancers12041058&pmid=32344707" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3390/cancers12041058" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/32344707" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B7-cancers-13-00043' class='html-x' data-content='7.'>Sivan, A.; Corrales, L.; Hubert, N.; Williams, J.B.; Aquino-Michaels, K.; Earley, Z.M.; Benyamin, F.W.; Lei, Y.M.; Jabri, B.; Alegre, M.L.; et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. <span class='html-italic'>Science</span> <b>2015</b>, <span class='html-italic'>350</span>, 1084–1089. [<a href="https://scholar.google.com/scholar_lookup?title=Commensal+Bifidobacterium+promotes+antitumor+immunity+and+facilitates+anti-PD-L1+efficacy&author=Sivan,+A.&author=Corrales,+L.&author=Hubert,+N.&author=Williams,+J.B.&author=Aquino-Michaels,+K.&author=Earley,+Z.M.&author=Benyamin,+F.W.&author=Lei,+Y.M.&author=Jabri,+B.&author=Alegre,+M.L.&publication_year=2015&journal=Science&volume=350&pages=1084%E2%80%931089&doi=10.1126/science.aac4255&pmid=26541606" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1126/science.aac4255" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/26541606" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://science.sciencemag.org/content/sci/350/6264/1084.full.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B8-cancers-13-00043' class='html-x' data-content='8.'>Derosa, L.; Routy, B.; Kroemer, G.; Zitvogel, L. The intestinal microbiota determines the clinical efficacy of immune checkpoint blockers targeting PD-1/PD-L1. <span class='html-italic'>Oncoimmunology</span> <b>2018</b>, <span class='html-italic'>7</span>, e1434468. [<a href="https://scholar.google.com/scholar_lookup?title=The+intestinal+microbiota+determines+the+clinical+efficacy+of+immune+checkpoint+blockers+targeting+PD-1/PD-L1&author=Derosa,+L.&author=Routy,+B.&author=Kroemer,+G.&author=Zitvogel,+L.&publication_year=2018&journal=Oncoimmunology&volume=7&pages=e1434468&doi=10.1080/2162402X.2018.1434468" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1080/2162402X.2018.1434468" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://www.tandfonline.com/doi/pdf/10.1080/2162402X.2018.1434468?needAccess=true" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B9-cancers-13-00043' class='html-x' data-content='9.'>Frankel, A.E.; Coughlin, L.A.; Kim, J.; Froehlich, T.W.; Xie, Y.; Frenkel, E.P.; Koh, A.Y. Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients. <span class='html-italic'>Neoplasia</span> <b>2017</b>, <span class='html-italic'>19</span>, 848–855. [<a href="https://scholar.google.com/scholar_lookup?title=Metagenomic+Shotgun+Sequencing+and+Unbiased+Metabolomic+Profiling+Identify+Specific+Human+Gut+Microbiota+and+Metabolites+Associated+with+Immune+Checkpoint+Therapy+Efficacy+in+Melanoma+Patients&author=Frankel,+A.E.&author=Coughlin,+L.A.&author=Kim,+J.&author=Froehlich,+T.W.&author=Xie,+Y.&author=Frenkel,+E.P.&author=Koh,+A.Y.&publication_year=2017&journal=Neoplasia&volume=19&pages=848%E2%80%93855&doi=10.1016/j.neo.2017.08.004" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.neo.2017.08.004" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B10-cancers-13-00043' class='html-xx' data-content='10.'>Gopalakrishnan, V.; Spencer, C.N.; Nezi, L.; Reuben, A.; Andrews, M.C.; Karpinets, T.V.; Prieto, P.A.; Vicente, D.; Hoffman, K.; Wei, S.C.; et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. <span class='html-italic'>Science</span> <b>2018</b>, <span class='html-italic'>359</span>, 97–103. [<a href="https://scholar.google.com/scholar_lookup?title=Gut+microbiome+modulates+response+to+anti-PD-1+immunotherapy+in+melanoma+patients&author=Gopalakrishnan,+V.&author=Spencer,+C.N.&author=Nezi,+L.&author=Reuben,+A.&author=Andrews,+M.C.&author=Karpinets,+T.V.&author=Prieto,+P.A.&author=Vicente,+D.&author=Hoffman,+K.&author=Wei,+S.C.&publication_year=2018&journal=Science&volume=359&pages=97%E2%80%93103&doi=10.1126/science.aan4236" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1126/science.aan4236" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://science.sciencemag.org/content/sci/359/6371/97.full.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B11-cancers-13-00043' class='html-xx' data-content='11.'>Dubin, K.; Callahan, M.K.; Ren, B.; Khanin, R.; Viale, A.; Ling, L.; No, D.; Gobourne, A.; Littmann, E.; Huttenhower, C.; et al. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis. <span class='html-italic'>Nat. Commun.</span> <b>2016</b>, <span class='html-italic'>7</span>, 10391. [<a href="https://scholar.google.com/scholar_lookup?title=Intestinal+microbiome+analyses+identify+melanoma+patients+at+risk+for+checkpoint-blockade-induced+colitis&author=Dubin,+K.&author=Callahan,+M.K.&author=Ren,+B.&author=Khanin,+R.&author=Viale,+A.&author=Ling,+L.&author=No,+D.&author=Gobourne,+A.&author=Littmann,+E.&author=Huttenhower,+C.&publication_year=2016&journal=Nat.+Commun.&volume=7&pages=10391&doi=10.1038/ncomms10391&pmid=26837003" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/ncomms10391" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/26837003" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://www.nature.com/articles/ncomms10391.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B12-cancers-13-00043' class='html-xx' data-content='12.'>Chaput, N.; Lepage, P.; Coutzac, C.; Soularue, E.; Le Roux, K.; Monot, C.; Boselli, L.; Routier, E.; Cassard, L.; Collins, M.; et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. <span class='html-italic'>Ann. Oncol.</span> <b>2017</b>, <span class='html-italic'>28</span>, 1368–1379. [<a href="https://scholar.google.com/scholar_lookup?title=Baseline+gut+microbiota+predicts+clinical+response+and+colitis+in+metastatic+melanoma+patients+treated+with+ipilimumab&author=Chaput,+N.&author=Lepage,+P.&author=Coutzac,+C.&author=Soularue,+E.&author=Le+Roux,+K.&author=Monot,+C.&author=Boselli,+L.&author=Routier,+E.&author=Cassard,+L.&author=Collins,+M.&publication_year=2017&journal=Ann.+Oncol.&volume=28&pages=1368%E2%80%931379&doi=10.1093/annonc/mdx108&pmid=28368458" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1093/annonc/mdx108" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/28368458" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B13-cancers-13-00043' class='html-xx' data-content='13.'>Kikuchi, T.; Mimura, K.; Ashizawa, M.; Okayama, H.; Endo, E.; Saito, K.; Sakamoto, W.; Fujita, S.; Endo, H.; Saito, M.; et al. Characterization of tumor-infiltrating immune cells in relation to microbiota in colorectal cancers. <span class='html-italic'>Cancer Immunol. Immunother.</span> <b>2020</b>, <span class='html-italic'>69</span>, 23–32. [<a href="https://scholar.google.com/scholar_lookup?title=Characterization+of+tumor-infiltrating+immune+cells+in+relation+to+microbiota+in+colorectal+cancers&author=Kikuchi,+T.&author=Mimura,+K.&author=Ashizawa,+M.&author=Okayama,+H.&author=Endo,+E.&author=Saito,+K.&author=Sakamoto,+W.&author=Fujita,+S.&author=Endo,+H.&author=Saito,+M.&publication_year=2020&journal=Cancer+Immunol.+Immunother.&volume=69&pages=23%E2%80%9332&doi=10.1007/s00262-019-02433-6&pmid=31768581" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1007/s00262-019-02433-6" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/31768581" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="http://ir.fmu.ac.jp/dspace/bitstream/123456789/983/1/Thesis_K642_review.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B14-cancers-13-00043' class='html-xx' data-content='14.'>Wrobel, P.; Ahmed, S. Current status of immunotherapy in metastatic colorectal cancer. <span class='html-italic'>Int. J. Colorectal Dis.</span> <b>2019</b>, <span class='html-italic'>34</span>, 13–25. [<a href="https://scholar.google.com/scholar_lookup?title=Current+status+of+immunotherapy+in+metastatic+colorectal+cancer&author=Wrobel,+P.&author=Ahmed,+S.&publication_year=2019&journal=Int.+J.+Colorectal+Dis.&volume=34&pages=13%E2%80%9325&doi=10.1007/s00384-018-3202-8" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1007/s00384-018-3202-8" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B15-cancers-13-00043' class='html-xx' data-content='15.'>Santhanam, S.; Alvarado, D.M.; Ciorba, M.A. Therapeutic targeting of inflammation and tryptophan metabolism in colon and gastrointestinal cancer. <span class='html-italic'>Transl. Res.</span> <b>2016</b>, <span class='html-italic'>167</span>, 67–79. [<a href="https://scholar.google.com/scholar_lookup?title=Therapeutic+targeting+of+inflammation+and+tryptophan+metabolism+in+colon+and+gastrointestinal+cancer&author=Santhanam,+S.&author=Alvarado,+D.M.&author=Ciorba,+M.A.&publication_year=2016&journal=Transl.+Res.&volume=167&pages=67%E2%80%9379&doi=10.1016/j.trsl.2015.07.003" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.trsl.2015.07.003" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://europepmc.org/articles/pmc4684437?pdf=render" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B16-cancers-13-00043' class='html-xx' data-content='16.'>Zhuo, Q.; Yu, B.; Zhou, J.; Zhang, J.; Zhang, R.; Xie, J.; Wang, Q.; Zhao, S. Lysates of Lactobacillus acidophilus combined with CTLA-4-blocking antibodies enhance antitumor immunity in a mouse colon cancer model. <span class='html-italic'>Sci. Rep.</span> <b>2019</b>, <span class='html-italic'>9</span>, 20128. [<a href="https://scholar.google.com/scholar_lookup?title=Lysates+of+Lactobacillus+acidophilus+combined+with+CTLA-4-blocking+antibodies+enhance+antitumor+immunity+in+a+mouse+colon+cancer+model&author=Zhuo,+Q.&author=Yu,+B.&author=Zhou,+J.&author=Zhang,+J.&author=Zhang,+R.&author=Xie,+J.&author=Wang,+Q.&author=Zhao,+S.&publication_year=2019&journal=Sci.+Rep.&volume=9&pages=20128&doi=10.1038/s41598-019-56661-y" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/s41598-019-56661-y" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B17-cancers-13-00043' class='html-xx' data-content='17.'>Xu, X.; Lv, J.; Guo, F.; Li, J.; Jia, Y.; Jiang, D.; Wang, N.; Zhang, C.; Kong, L.; Liu, Y.; et al. Gut Microbiome Influences the Efficacy of PD-1 Antibody Immunotherapy on MSS-Type Colorectal Cancer via Metabolic Pathway. <span class='html-italic'>Front. Microbiol.</span> <b>2020</b>, <span class='html-italic'>11</span>, 814. [<a href="https://scholar.google.com/scholar_lookup?title=Gut+Microbiome+Influences+the+Efficacy+of+PD-1+Antibody+Immunotherapy+on+MSS-Type+Colorectal+Cancer+via+Metabolic+Pathway&author=Xu,+X.&author=Lv,+J.&author=Guo,+F.&author=Li,+J.&author=Jia,+Y.&author=Jiang,+D.&author=Wang,+N.&author=Zhang,+C.&author=Kong,+L.&author=Liu,+Y.&publication_year=2020&journal=Front.+Microbiol.&volume=11&pages=814&doi=10.3389/fmicb.2020.00814" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3389/fmicb.2020.00814" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B18-cancers-13-00043' class='html-xx' data-content='18.'>Mariotto, A.B.; Yabroff, K.R.; Shao, Y.; Feuer, E.J.; Brown, M.L. Projections of the cost of cancer care in the United States: 2010–2020. <span class='html-italic'>J. Natl. Cancer Inst.</span> <b>2011</b>, <span class='html-italic'>103</span>, 117–128. [<a href="https://scholar.google.com/scholar_lookup?title=Projections+of+the+cost+of+cancer+care+in+the+United+States:+2010%E2%80%932020&author=Mariotto,+A.B.&author=Yabroff,+K.R.&author=Shao,+Y.&author=Feuer,+E.J.&author=Brown,+M.L.&publication_year=2011&journal=J.+Natl.+Cancer+Inst.&volume=103&pages=117%E2%80%93128&doi=10.1093/jnci/djq495" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1093/jnci/djq495" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://academic.oup.com/jnci/article-pdf/103/2/117/7904809/djq495.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B19-cancers-13-00043' class='html-xx' data-content='19.'>Le, D.T.; Uram, J.N.; Wang, H.; Bartlett, B.R.; Kemberling, H.; Eyring, A.D.; Skora, A.D.; Luber, B.S.; Azad, N.S.; Laheru, D.; et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. <span class='html-italic'>N. Engl. J. Med.</span> <b>2015</b>, <span class='html-italic'>372</span>, 2509–2520. [<a href="https://scholar.google.com/scholar_lookup?title=PD-1+Blockade+in+Tumors+with+Mismatch-Repair+Deficiency&author=Le,+D.T.&author=Uram,+J.N.&author=Wang,+H.&author=Bartlett,+B.R.&author=Kemberling,+H.&author=Eyring,+A.D.&author=Skora,+A.D.&author=Luber,+B.S.&author=Azad,+N.S.&author=Laheru,+D.&publication_year=2015&journal=N.+Engl.+J.+Med.&volume=372&pages=2509%E2%80%932520&doi=10.1056/NEJMoa1500596" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1056/NEJMoa1500596" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B20-cancers-13-00043' class='html-xx' data-content='20.'>Overman, M.J.; McDermott, R.; Leach, J.L.; Lonardi, S.; Lenz, H.J.; Morse, M.A.; Desai, J.; Hill, A.; Axelson, M.; Moss, R.A.; et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): An open-label, multicentre, phase 2 study. <span class='html-italic'>Lancet Oncol.</span> <b>2017</b>, <span class='html-italic'>18</span>, 1182–1191. [<a href="https://scholar.google.com/scholar_lookup?title=Nivolumab+in+patients+with+metastatic+DNA+mismatch+repair-deficient+or+microsatellite+instability-high+colorectal+cancer+(CheckMate+142):+An+open-label,+multicentre,+phase+2+study&author=Overman,+M.J.&author=McDermott,+R.&author=Leach,+J.L.&author=Lonardi,+S.&author=Lenz,+H.J.&author=Morse,+M.A.&author=Desai,+J.&author=Hill,+A.&author=Axelson,+M.&author=Moss,+R.A.&publication_year=2017&journal=Lancet+Oncol.&volume=18&pages=1182%E2%80%931191&doi=10.1016/S1470-2045(17)30422-9" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/S1470-2045(17)30422-9" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B21-cancers-13-00043' class='html-xx' data-content='21.'>Boland, C.R.; Goel, A. Microsatellite instability in colorectal cancer. <span class='html-italic'>Gastroenterology</span> <b>2010</b>, <span class='html-italic'>138</span>, 2073–2087. [<a href="https://scholar.google.com/scholar_lookup?title=Microsatellite+instability+in+colorectal+cancer&author=Boland,+C.R.&author=Goel,+A.&publication_year=2010&journal=Gastroenterology&volume=138&pages=2073%E2%80%932087&doi=10.1053/j.gastro.2009.12.064&pmid=20420947" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1053/j.gastro.2009.12.064" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/20420947" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B22-cancers-13-00043' class='html-xx' data-content='22.'>Poulogiannis, G.; Frayling, I.M.; Arends, M.J. DNA mismatch repair deficiency in sporadic colorectal cancer and Lynch syndrome. <span class='html-italic'>Histopathology</span> <b>2010</b>, <span class='html-italic'>56</span>, 167–179. [<a href="https://scholar.google.com/scholar_lookup?title=DNA+mismatch+repair+deficiency+in+sporadic+colorectal+cancer+and+Lynch+syndrome&author=Poulogiannis,+G.&author=Frayling,+I.M.&author=Arends,+M.J.&publication_year=2010&journal=Histopathology&volume=56&pages=167%E2%80%93179&doi=10.1111/j.1365-2559.2009.03392.x&pmid=20102395" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1111/j.1365-2559.2009.03392.x" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/20102395" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://hal.archives-ouvertes.fr/hal-00549900/file/PEER_stage2_10.1111%2Fj.1365-2559.2009.03392.x.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B23-cancers-13-00043' class='html-xx' data-content='23.'>Ingram, J.R.; Blomberg, O.S.; Rashidian, M.; Ali, L.; Garforth, S.; Fedorov, E.; Fedorov, A.A.; Bonanno, J.B.; Le Gall, C.; Crowley, S.; et al. Anti-CTLA-4 therapy requires an Fc domain for efficacy. <span class='html-italic'>Proc. Natl. Acad. Sci. USA</span> <b>2018</b>, <span class='html-italic'>115</span>, 3912–3917. [<a href="https://scholar.google.com/scholar_lookup?title=Anti-CTLA-4+therapy+requires+an+Fc+domain+for+efficacy&author=Ingram,+J.R.&author=Blomberg,+O.S.&author=Rashidian,+M.&author=Ali,+L.&author=Garforth,+S.&author=Fedorov,+E.&author=Fedorov,+A.A.&author=Bonanno,+J.B.&author=Le+Gall,+C.&author=Crowley,+S.&publication_year=2018&journal=Proc.+Natl.+Acad.+Sci.+USA&volume=115&pages=3912%E2%80%933917&doi=10.1073/pnas.1801524115&pmid=29581255" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1073/pnas.1801524115" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/29581255" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://www.pnas.org/content/pnas/115/15/3912.full.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B24-cancers-13-00043' class='html-xx' data-content='24.'>Frankel, A.E.; Deshmukh, S.; Reddy, A.; Lightcap, J.; Hayes, M.; McClellan, S.; Singh, S.; Rabideau, B.; Glover, T.G.; Roberts, B.; et al. Cancer Immune Checkpoint Inhibitor Therapy and the Gut Microbiota. <span class='html-italic'>Integr. Cancer Ther.</span> <b>2019</b>, <span class='html-italic'>18</span>, 1534735419846379. [<a href="https://scholar.google.com/scholar_lookup?title=Cancer+Immune+Checkpoint+Inhibitor+Therapy+and+the+Gut+Microbiota&author=Frankel,+A.E.&author=Deshmukh,+S.&author=Reddy,+A.&author=Lightcap,+J.&author=Hayes,+M.&author=McClellan,+S.&author=Singh,+S.&author=Rabideau,+B.&author=Glover,+T.G.&author=Roberts,+B.&publication_year=2019&journal=Integr.+Cancer+Ther.&volume=18&pages=1534735419846379&doi=10.1177/1534735419846379&pmid=31014119" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1177/1534735419846379" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/31014119" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B25-cancers-13-00043' class='html-xx' data-content='25.'>Garris, C.S.; Arlauckas, S.P.; Kohler, R.H.; Trefny, M.P.; Garren, S.; Piot, C.; Engblom, C.; Pfirschke, C.; Siwicki, M.; Gungabeesoon, J.; et al. Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-gamma and IL-12. <span class='html-italic'>Immunity</span> <b>2018</b>, <span class='html-italic'>49</span>, 1148–1161. [<a href="https://scholar.google.com/scholar_lookup?title=Successful+Anti-PD-1+Cancer+Immunotherapy+Requires+T+Cell-Dendritic+Cell+Crosstalk+Involving+the+Cytokines+IFN-gamma+and+IL-12&author=Garris,+C.S.&author=Arlauckas,+S.P.&author=Kohler,+R.H.&author=Trefny,+M.P.&author=Garren,+S.&author=Piot,+C.&author=Engblom,+C.&author=Pfirschke,+C.&author=Siwicki,+M.&author=Gungabeesoon,+J.&publication_year=2018&journal=Immunity&volume=49&pages=1148%E2%80%931161&doi=10.1016/j.immuni.2018.09.024" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.immuni.2018.09.024" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.cell.com/article/S1074761318304394/pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B26-cancers-13-00043' class='html-xx' data-content='26.'>Li, W.; Deng, Y.; Chu, Q.; Zhang, P. Gut microbiome and cancer immunotherapy. <span class='html-italic'>Cancer Lett.</span> <b>2019</b>, <span class='html-italic'>447</span>, 41–47. [<a href="https://scholar.google.com/scholar_lookup?title=Gut+microbiome+and+cancer+immunotherapy&author=Li,+W.&author=Deng,+Y.&author=Chu,+Q.&author=Zhang,+P.&publication_year=2019&journal=Cancer+Lett.&volume=447&pages=41%E2%80%9347&doi=10.1016/j.canlet.2019.01.015" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.canlet.2019.01.015" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B27-cancers-13-00043' class='html-xx' data-content='27.'>Gandini, S.; Massi, D.; Mandala, M. PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis. <span class='html-italic'>Crit. Rev. Oncol. Hematol.</span> <b>2016</b>, <span class='html-italic'>100</span>, 88–98. [<a href="https://scholar.google.com/scholar_lookup?title=PD-L1+expression+in+cancer+patients+receiving+anti+PD-1/PD-L1+antibodies:+A+systematic+review+and+meta-analysis&author=Gandini,+S.&author=Massi,+D.&author=Mandala,+M.&publication_year=2016&journal=Crit.+Rev.+Oncol.+Hematol.&volume=100&pages=88%E2%80%9398&doi=10.1016/j.critrevonc.2016.02.001" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.critrevonc.2016.02.001" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B28-cancers-13-00043' class='html-xx' data-content='28.'>Koustas, E.; Sarantis, P.; Papavassiliou, A.G.; Karamouzis, M.V. The Resistance Mechanisms of Checkpoint Inhibitors in Solid Tumors. <span class='html-italic'>Biomolecules</span> <b>2020</b>, <span class='html-italic'>10</span>, 666. [<a href="https://scholar.google.com/scholar_lookup?title=The+Resistance+Mechanisms+of+Checkpoint+Inhibitors+in+Solid+Tumors&author=Koustas,+E.&author=Sarantis,+P.&author=Papavassiliou,+A.G.&author=Karamouzis,+M.V.&publication_year=2020&journal=Biomolecules&volume=10&pages=666&doi=10.3390/biom10050666" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3390/biom10050666" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B29-cancers-13-00043' class='html-xx' data-content='29.'>Kim, J.H.; Kim, B.S.; Lee, S.K. Regulatory T Cells in Tumor Microenvironment and Approach for Anticancer Immunotherapy. <span class='html-italic'>Immune Netw.</span> <b>2020</b>, <span class='html-italic'>20</span>, e4. [<a href="https://scholar.google.com/scholar_lookup?title=Regulatory+T+Cells+in+Tumor+Microenvironment+and+Approach+for+Anticancer+Immunotherapy&author=Kim,+J.H.&author=Kim,+B.S.&author=Lee,+S.K.&publication_year=2020&journal=Immune+Netw.&volume=20&pages=e4&doi=10.4110/in.2020.20.e4" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.4110/in.2020.20.e4" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B30-cancers-13-00043' class='html-xx' data-content='30.'>DiLillo, D.J.; Matsushita, T.; Tedder, T.F. B10 cells and regulatory B cells balance immune responses during inflammation, autoimmunity, and cancer. <span class='html-italic'>Ann. N. Y. Acad. Sci.</span> <b>2010</b>, <span class='html-italic'>1183</span>, 38–57. [<a href="https://scholar.google.com/scholar_lookup?title=B10+cells+and+regulatory+B+cells+balance+immune+responses+during+inflammation,+autoimmunity,+and+cancer&author=DiLillo,+D.J.&author=Matsushita,+T.&author=Tedder,+T.F.&publication_year=2010&journal=Ann.+N.+Y.+Acad.+Sci.&volume=1183&pages=38%E2%80%9357&doi=10.1111/j.1749-6632.2009.05137.x" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1111/j.1749-6632.2009.05137.x" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B31-cancers-13-00043' class='html-xx' data-content='31.'>Dysthe, M.; Parihar, R. Myeloid-Derived Suppressor Cells in the Tumor Microenvironment. <span class='html-italic'>Adv. Exp. Med. Biol.</span> <b>2020</b>, <span class='html-italic'>1224</span>, 117–140. [<a href="https://scholar.google.com/scholar_lookup?title=Myeloid-Derived+Suppressor+Cells+in+the+Tumor+Microenvironment&author=Dysthe,+M.&author=Parihar,+R.&publication_year=2020&journal=Adv.+Exp.+Med.+Biol.&volume=1224&pages=117%E2%80%93140&doi=10.1007/978-3-030-35723-8_8&pmid=32036608" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1007/978-3-030-35723-8_8" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/32036608" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B32-cancers-13-00043' class='html-xx' data-content='32.'>Jayasingam, S.D.; Citartan, M.; Thang, T.H.; Mat Zin, A.A.; Ang, K.C.; Ch’ng, E.S. Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice. <span class='html-italic'>Front. Oncol.</span> <b>2020</b>, <span class='html-italic'>9</span>, 1512. [<a href="https://scholar.google.com/scholar_lookup?title=Evaluating+the+Polarization+of+Tumor-Associated+Macrophages+Into+M1+and+M2+Phenotypes+in+Human+Cancer+Tissue:+Technicalities+and+Challenges+in+Routine+Clinical+Practice&author=Jayasingam,+S.D.&author=Citartan,+M.&author=Thang,+T.H.&author=Mat+Zin,+A.A.&author=Ang,+K.C.&author=Ch%E2%80%99ng,+E.S.&publication_year=2020&journal=Front.+Oncol.&volume=9&pages=1512&doi=10.3389/fonc.2019.01512&pmid=32039007" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3389/fonc.2019.01512" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/32039007" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://www.frontiersin.org/articles/10.3389/fonc.2019.01512/pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B33-cancers-13-00043' class='html-xx' data-content='33.'>Zhou, J.; Tang, Z.; Gao, S.; Li, C.; Feng, Y.; Zhou, X. Tumor-Associated Macrophages: Recent Insights and Therapies. <span class='html-italic'>Front. Oncol.</span> <b>2020</b>, <span class='html-italic'>10</span>, 188. [<a href="https://scholar.google.com/scholar_lookup?title=Tumor-Associated+Macrophages:+Recent+Insights+and+Therapies&author=Zhou,+J.&author=Tang,+Z.&author=Gao,+S.&author=Li,+C.&author=Feng,+Y.&author=Zhou,+X.&publication_year=2020&journal=Front.+Oncol.&volume=10&pages=188&doi=10.3389/fonc.2020.00188&pmid=32161718" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3389/fonc.2020.00188" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/32161718" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B34-cancers-13-00043' class='html-xx' data-content='34.'>Maciel, T.T.; Moura, I.C.; Hermine, O. The role of mast cells in cancers. <span class='html-italic'>F1000Prime Rep.</span> <b>2015</b>, <span class='html-italic'>7</span>, 09. [<a href="https://scholar.google.com/scholar_lookup?title=The+role+of+mast+cells+in+cancers&author=Maciel,+T.T.&author=Moura,+I.C.&author=Hermine,+O.&publication_year=2015&journal=F1000Prime+Rep.&volume=7&pages=09&doi=10.12703/P7-09" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.12703/P7-09" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B35-cancers-13-00043' class='html-xx' data-content='35.'>Yun, C.W.; Lee, S.H. The Roles of Autophagy in Cancer. <span class='html-italic'>Int. J. Mol. Sci.</span> <b>2018</b>, <span class='html-italic'>19</span>, 3466. [<a href="https://scholar.google.com/scholar_lookup?title=The+Roles+of+Autophagy+in+Cancer&author=Yun,+C.W.&author=Lee,+S.H.&publication_year=2018&journal=Int.+J.+Mol.+Sci.&volume=19&pages=3466&doi=10.3390/ijms19113466&pmid=30400561" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3390/ijms19113466" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/30400561" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://www.mdpi.com/1422-0067/19/11/3466/pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B36-cancers-13-00043' class='html-xx' data-content='36.'>Crotzer, V.L.; Blum, J.S. Autophagy and its role in MHC-mediated antigen presentation. <span class='html-italic'>J. Immunol.</span> <b>2009</b>, <span class='html-italic'>182</span>, 3335–3341. [<a href="https://scholar.google.com/scholar_lookup?title=Autophagy+and+its+role+in+MHC-mediated+antigen+presentation&author=Crotzer,+V.L.&author=Blum,+J.S.&publication_year=2009&journal=J.+Immunol.&volume=182&pages=3335%E2%80%933341&doi=10.4049/jimmunol.0803458" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.4049/jimmunol.0803458" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://www.jimmunol.org/content/jimmunol/182/6/3335.full.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B37-cancers-13-00043' class='html-xx' data-content='37.'>Castle, J.C.; Uduman, M.; Pabla, S.; Stein, R.B.; Buell, J.S. Mutation-Derived Neoantigens for Cancer Immunotherapy. <span class='html-italic'>Front. Immunol.</span> <b>2019</b>, <span class='html-italic'>10</span>, 1856. [<a href="https://scholar.google.com/scholar_lookup?title=Mutation-Derived+Neoantigens+for+Cancer+Immunotherapy&author=Castle,+J.C.&author=Uduman,+M.&author=Pabla,+S.&author=Stein,+R.B.&author=Buell,+J.S.&publication_year=2019&journal=Front.+Immunol.&volume=10&pages=1856&doi=10.3389/fimmu.2019.01856" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3389/fimmu.2019.01856" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://www.frontiersin.org/articles/10.3389/fimmu.2019.01856/pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B38-cancers-13-00043' class='html-xx' data-content='38.'>Johnson, C.H.; Spilker, M.E.; Goetz, L.; Peterson, S.N.; Siuzdak, G. Metabolite and Microbiome Interplay in Cancer Immunotherapy. <span class='html-italic'>Cancer Res.</span> <b>2016</b>, <span class='html-italic'>76</span>, 6146–6152. [<a href="https://scholar.google.com/scholar_lookup?title=Metabolite+and+Microbiome+Interplay+in+Cancer+Immunotherapy&author=Johnson,+C.H.&author=Spilker,+M.E.&author=Goetz,+L.&author=Peterson,+S.N.&author=Siuzdak,+G.&publication_year=2016&journal=Cancer+Res.&volume=76&pages=6146%E2%80%936152&doi=10.1158/0008-5472.CAN-16-0309" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1158/0008-5472.CAN-16-0309" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://cancerres.aacrjournals.org/content/canres/76/21/6146.full.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B39-cancers-13-00043' class='html-xx' data-content='39.'>Alegre, M.L.; Bromberg, J.S. Commensal microbiota determine intestinal iTreg. <span class='html-italic'>Am. J. Transplant.</span> <b>2012</b>, <span class='html-italic'>12</span>, 1967. [<a href="https://scholar.google.com/scholar_lookup?title=Commensal+microbiota+determine+intestinal+iTreg&author=Alegre,+M.L.&author=Bromberg,+J.S.&publication_year=2012&journal=Am.+J.+Transplant.&volume=12&pages=1967&doi=10.1111/j.1600-6143.2012.04217.x" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1111/j.1600-6143.2012.04217.x" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B40-cancers-13-00043' class='html-xx' data-content='40.'>Weersma, R.K.; Zhernakova, A.; Fu, J. Interaction between drugs and the gut microbiome. <span class='html-italic'>Gut</span> <b>2020</b>, <span class='html-italic'>69</span>, 1510–1519. [<a href="https://scholar.google.com/scholar_lookup?title=Interaction+between+drugs+and+the+gut+microbiome&author=Weersma,+R.K.&author=Zhernakova,+A.&author=Fu,+J.&publication_year=2020&journal=Gut&volume=69&pages=1510%E2%80%931519&doi=10.1136/gutjnl-2019-320204" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1136/gutjnl-2019-320204" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B41-cancers-13-00043' class='html-xx' data-content='41.'>Zeromski, J.; Kaczmarek, M.; Boruczkowski, M.; Kierepa, A.; Kowala-Piaskowska, A.; Mozer-Lisewska, I. Significance and Role of Pattern Recognition Receptors in Malignancy. <span class='html-italic'>Arch. Immunol. Ther. Exp.</span> <b>2019</b>, <span class='html-italic'>67</span>, 133–141. [<a href="https://scholar.google.com/scholar_lookup?title=Significance+and+Role+of+Pattern+Recognition+Receptors+in+Malignancy&author=Zeromski,+J.&author=Kaczmarek,+M.&author=Boruczkowski,+M.&author=Kierepa,+A.&author=Kowala-Piaskowska,+A.&author=Mozer-Lisewska,+I.&publication_year=2019&journal=Arch.+Immunol.+Ther.+Exp.&volume=67&pages=133%E2%80%93141&doi=10.1007/s00005-019-00540-x&pmid=30976817" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1007/s00005-019-00540-x" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/30976817" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://link.springer.com/content/pdf/10.1007/s00005-019-00540-x.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B42-cancers-13-00043' class='html-xx' data-content='42.'>Dai, Z.; Zhang, J.; Wu, Q.; Fang, H.; Shi, C.; Li, Z.; Lin, C.; Tang, D.; Wang, D. Intestinal microbiota: A new force in cancer immunotherapy. <span class='html-italic'>Cell Commun. Signal.</span> <b>2020</b>, <span class='html-italic'>18</span>, 90. [<a href="https://scholar.google.com/scholar_lookup?title=Intestinal+microbiota:+A+new+force+in+cancer+immunotherapy&author=Dai,+Z.&author=Zhang,+J.&author=Wu,+Q.&author=Fang,+H.&author=Shi,+C.&author=Li,+Z.&author=Lin,+C.&author=Tang,+D.&author=Wang,+D.&publication_year=2020&journal=Cell+Commun.+Signal.&volume=18&pages=90&doi=10.1186/s12964-020-00599-6&pmid=32522267" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1186/s12964-020-00599-6" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/32522267" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B43-cancers-13-00043' class='html-xx' data-content='43.'>Shcheblyakov, D.V.; Logunov, D.Y.; Tukhvatulin, A.I.; Shmarov, M.M.; Naroditsky, B.S.; Gintsburg, A.L. Toll-Like Receptors (TLRs): The Role in Tumor Progression. <span class='html-italic'>Acta Nat.</span> <b>2010</b>, <span class='html-italic'>2</span>, 21–29. [<a href="https://scholar.google.com/scholar_lookup?title=Toll-Like+Receptors+(TLRs):+The+Role+in+Tumor+Progression&author=Shcheblyakov,+D.V.&author=Logunov,+D.Y.&author=Tukhvatulin,+A.I.&author=Shmarov,+M.M.&author=Naroditsky,+B.S.&author=Gintsburg,+A.L.&publication_year=2010&journal=Acta+Nat.&volume=2&pages=21%E2%80%9329&doi=10.32607/20758251-2010-2-3-21-29" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.32607/20758251-2010-2-3-21-29" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://pdfs.semanticscholar.org/e388/c707411044f473d20bbb87c578fad15de2d2.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B44-cancers-13-00043' class='html-xx' data-content='44.'>Coker, O.O.; Nakatsu, G.; Dai, R.Z.; Wu, W.K.K.; Wong, S.H.; Ng, S.C.; Chan, F.K.L.; Sung, J.J.Y.; Yu, J. Enteric fungal microbiota dysbiosis and ecological alterations in colorectal cancer. <span class='html-italic'>Gut</span> <b>2019</b>, <span class='html-italic'>68</span>, 654–662. [<a href="https://scholar.google.com/scholar_lookup?title=Enteric+fungal+microbiota+dysbiosis+and+ecological+alterations+in+colorectal+cancer&author=Coker,+O.O.&author=Nakatsu,+G.&author=Dai,+R.Z.&author=Wu,+W.K.K.&author=Wong,+S.H.&author=Ng,+S.C.&author=Chan,+F.K.L.&author=Sung,+J.J.Y.&author=Yu,+J.&publication_year=2019&journal=Gut&volume=68&pages=654%E2%80%93662&doi=10.1136/gutjnl-2018-317178&pmid=30472682" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1136/gutjnl-2018-317178" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/30472682" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B45-cancers-13-00043' class='html-xx' data-content='45.'>Urban-Wojciuk, Z.; Khan, M.M.; Oyler, B.L.; Fahraeus, R.; Marek-Trzonkowska, N.; Nita-Lazar, A.; Hupp, T.R.; Goodlett, D.R. The Role of TLRs in Anti-cancer Immunity and Tumor Rejection. <span class='html-italic'>Front. Immunol.</span> <b>2019</b>, <span class='html-italic'>10</span>, 2388. [<a href="https://scholar.google.com/scholar_lookup?title=The+Role+of+TLRs+in+Anti-cancer+Immunity+and+Tumor+Rejection&author=Urban-Wojciuk,+Z.&author=Khan,+M.M.&author=Oyler,+B.L.&author=Fahraeus,+R.&author=Marek-Trzonkowska,+N.&author=Nita-Lazar,+A.&author=Hupp,+T.R.&author=Goodlett,+D.R.&publication_year=2019&journal=Front.+Immunol.&volume=10&pages=2388&doi=10.3389/fimmu.2019.02388" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3389/fimmu.2019.02388" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B46-cancers-13-00043' class='html-xx' data-content='46.'>Wang, L.; Yu, K.; Zhang, X.; Yu, S. Dual functional roles of the MyD88 signaling in colorectal cancer development. <span class='html-italic'>Biomed. Pharmacother.</span> <b>2018</b>, <span class='html-italic'>107</span>, 177–184. [<a href="https://scholar.google.com/scholar_lookup?title=Dual+functional+roles+of+the+MyD88+signaling+in+colorectal+cancer+development&author=Wang,+L.&author=Yu,+K.&author=Zhang,+X.&author=Yu,+S.&publication_year=2018&journal=Biomed.+Pharmacother.&volume=107&pages=177%E2%80%93184&doi=10.1016/j.biopha.2018.07.139" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.biopha.2018.07.139" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B47-cancers-13-00043' class='html-xx' data-content='47.'>Lavelle, E.C.; Murphy, C.; O’Neill, L.A.; Creagh, E.M. The role of TLRs, NLRs, and RLRs in mucosal innate immunity and homeostasis. <span class='html-italic'>Mucosal Immunol.</span> <b>2010</b>, <span class='html-italic'>3</span>, 17–28. [<a href="https://scholar.google.com/scholar_lookup?title=The+role+of+TLRs,+NLRs,+and+RLRs+in+mucosal+innate+immunity+and+homeostasis&author=Lavelle,+E.C.&author=Murphy,+C.&author=O%E2%80%99Neill,+L.A.&author=Creagh,+E.M.&publication_year=2010&journal=Mucosal+Immunol.&volume=3&pages=17%E2%80%9328&doi=10.1038/mi.2009.124" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/mi.2009.124" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://www.nature.com/articles/mi2009124.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B48-cancers-13-00043' class='html-xx' data-content='48.'>Miao, E.A.; Andersen-Nissen, E.; Warren, S.E.; Aderem, A. TLR5 and Ipaf: Dual sensors of bacterial flagellin in the innate immune system. <span class='html-italic'>Semin. Immunopathol.</span> <b>2007</b>, <span class='html-italic'>29</span>, 275–288. [<a href="https://scholar.google.com/scholar_lookup?title=TLR5+and+Ipaf:+Dual+sensors+of+bacterial+flagellin+in+the+innate+immune+system&author=Miao,+E.A.&author=Andersen-Nissen,+E.&author=Warren,+S.E.&author=Aderem,+A.&publication_year=2007&journal=Semin.+Immunopathol.&volume=29&pages=275%E2%80%93288&doi=10.1007/s00281-007-0078-z" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1007/s00281-007-0078-z" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B49-cancers-13-00043' class='html-xx' data-content='49.'>Kawai, T.; Akira, S. The roles of TLRs, RLRs and NLRs in pathogen recognition. <span class='html-italic'>Int. Immunol.</span> <b>2009</b>, <span class='html-italic'>21</span>, 317–337. [<a href="https://scholar.google.com/scholar_lookup?title=The+roles+of+TLRs,+RLRs+and+NLRs+in+pathogen+recognition&author=Kawai,+T.&author=Akira,+S.&publication_year=2009&journal=Int.+Immunol.&volume=21&pages=317%E2%80%93337&doi=10.1093/intimm/dxp017" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1093/intimm/dxp017" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://academic.oup.com/intimm/article-pdf/21/4/317/2204429/dxp017.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B50-cancers-13-00043' class='html-xx' data-content='50.'>Monie, T.P.; Bryant, C.E.; Gay, N.J. Activating immunity: Lessons from the TLRs and NLRs. <span class='html-italic'>Trends Biochem. Sci.</span> <b>2009</b>, <span class='html-italic'>34</span>, 553–561. [<a href="https://scholar.google.com/scholar_lookup?title=Activating+immunity:+Lessons+from+the+TLRs+and+NLRs&author=Monie,+T.P.&author=Bryant,+C.E.&author=Gay,+N.J.&publication_year=2009&journal=Trends+Biochem.+Sci.&volume=34&pages=553%E2%80%93561&doi=10.1016/j.tibs.2009.06.011" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.tibs.2009.06.011" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B51-cancers-13-00043' class='html-xx' data-content='51.'>Haabeth, O.A.W.; Fauskanger, M.; Manzke, M.; Lundin, K.U.; Corthay, A.; Bogen, B.; Tveita, A.A. CD4(+) T-cell-Mediated Rejection of MHC Class II-Positive Tumor Cells Is Dependent on Antigen Secretion and Indirect Presentation on Host APCs. <span class='html-italic'>Cancer Res.</span> <b>2018</b>, <span class='html-italic'>78</span>, 4573–4585. [<a href="https://scholar.google.com/scholar_lookup?title=CD4(+)+T-cell-Mediated+Rejection+of+MHC+Class+II-Positive+Tumor+Cells+Is+Dependent+on+Antigen+Secretion+and+Indirect+Presentation+on+Host+APCs&author=Haabeth,+O.A.W.&author=Fauskanger,+M.&author=Manzke,+M.&author=Lundin,+K.U.&author=Corthay,+A.&author=Bogen,+B.&author=Tveita,+A.A.&publication_year=2018&journal=Cancer+Res.&volume=78&pages=4573%E2%80%934585&doi=10.1158/0008-5472.CAN-17-2426&pmid=29752262" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1158/0008-5472.CAN-17-2426" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/29752262" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://cancerres.aacrjournals.org/content/canres/78/16/4573.full.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B52-cancers-13-00043' class='html-xx' data-content='52.'>Grosserichter-Wagener, C.; Radjabzadeh, D.; van der Weide, H.; Smit, K.N.; Kraaij, R.; Hays, J.P.; van Zelm, M.C. Differences in Systemic IgA Reactivity and Circulating Th Subsets in Healthy Volunteers With Specific Microbiota Enterotypes. <span class='html-italic'>Front. Immunol.</span> <b>2019</b>, <span class='html-italic'>10</span>, 341. [<a href="https://scholar.google.com/scholar_lookup?title=Differences+in+Systemic+IgA+Reactivity+and+Circulating+Th+Subsets+in+Healthy+Volunteers+With+Specific+Microbiota+Enterotypes&author=Grosserichter-Wagener,+C.&author=Radjabzadeh,+D.&author=van+der+Weide,+H.&author=Smit,+K.N.&author=Kraaij,+R.&author=Hays,+J.P.&author=van+Zelm,+M.C.&publication_year=2019&journal=Front.+Immunol.&volume=10&pages=341&doi=10.3389/fimmu.2019.00341&pmid=30899257" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3389/fimmu.2019.00341" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/30899257" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B53-cancers-13-00043' class='html-xx' data-content='53.'>Maruya, M.; Kawamoto, S.; Kato, L.M.; Fagarasan, S. Impaired selection of IgA and intestinal dysbiosis associated with PD-1-deficiency. <span class='html-italic'>Gut Microbes</span> <b>2013</b>, <span class='html-italic'>4</span>, 165–171. [<a href="https://scholar.google.com/scholar_lookup?title=Impaired+selection+of+IgA+and+intestinal+dysbiosis+associated+with+PD-1-deficiency&author=Maruya,+M.&author=Kawamoto,+S.&author=Kato,+L.M.&author=Fagarasan,+S.&publication_year=2013&journal=Gut+Microbes&volume=4&pages=165%E2%80%93171&doi=10.4161/gmic.23595&pmid=23333864" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.4161/gmic.23595" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/23333864" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="http://europepmc.org/articles/pmc3595078?pdf=render" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B54-cancers-13-00043' class='html-xx' data-content='54.'>Kawamoto, S.; Tran, T.H.; Maruya, M.; Suzuki, K.; Doi, Y.; Tsutsui, Y.; Kato, L.M.; Fagarasan, S. The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut. <span class='html-italic'>Science</span> <b>2012</b>, <span class='html-italic'>336</span>, 485–489. [<a href="https://scholar.google.com/scholar_lookup?title=The+inhibitory+receptor+PD-1+regulates+IgA+selection+and+bacterial+composition+in+the+gut&author=Kawamoto,+S.&author=Tran,+T.H.&author=Maruya,+M.&author=Suzuki,+K.&author=Doi,+Y.&author=Tsutsui,+Y.&author=Kato,+L.M.&author=Fagarasan,+S.&publication_year=2012&journal=Science&volume=336&pages=485%E2%80%93489&doi=10.1126/science.1217718&pmid=22539724" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1126/science.1217718" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/22539724" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B55-cancers-13-00043' class='html-xx' data-content='55.'>Kuen, D.S.; Kim, B.S.; Chung, Y. IL-17-Producing Cells in Tumor Immunity: Friends or Foes? <span class='html-italic'>Immune Netw.</span> <b>2020</b>, <span class='html-italic'>20</span>, e6. [<a href="https://scholar.google.com/scholar_lookup?title=IL-17-Producing+Cells+in+Tumor+Immunity:+Friends+or+Foes?&author=Kuen,+D.S.&author=Kim,+B.S.&author=Chung,+Y.&publication_year=2020&journal=Immune+Netw.&volume=20&pages=e6&doi=10.4110/in.2020.20.e6" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.4110/in.2020.20.e6" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B56-cancers-13-00043' class='html-xx' data-content='56.'>Razi, S.; Baradaran Noveiry, B.; Keshavarz-Fathi, M.; Rezaei, N. IL-17 and colorectal cancer: From carcinogenesis to treatment. <span class='html-italic'>Cytokine</span> <b>2019</b>, <span class='html-italic'>116</span>, 7–12. [<a href="https://scholar.google.com/scholar_lookup?title=IL-17+and+colorectal+cancer:+From+carcinogenesis+to+treatment&author=Razi,+S.&author=Baradaran+Noveiry,+B.&author=Keshavarz-Fathi,+M.&author=Rezaei,+N.&publication_year=2019&journal=Cytokine&volume=116&pages=7%E2%80%9312&doi=10.1016/j.cyto.2018.12.021" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.cyto.2018.12.021" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B57-cancers-13-00043' class='html-xx' data-content='57.'>Khazaie, K.; von Boehmer, H. The impact of CD4+CD25+ Treg on tumor specific CD8+ T cell cytotoxicity and cancer. <span class='html-italic'>Semin. Cancer Biol.</span> <b>2006</b>, <span class='html-italic'>16</span>, 124–136. [<a href="https://scholar.google.com/scholar_lookup?title=The+impact+of+CD4+CD25++Treg+on+tumor+specific+CD8++T+cell+cytotoxicity+and+cancer&author=Khazaie,+K.&author=von+Boehmer,+H.&publication_year=2006&journal=Semin.+Cancer+Biol.&volume=16&pages=124%E2%80%93136&doi=10.1016/j.semcancer.2005.11.006" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.semcancer.2005.11.006" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B58-cancers-13-00043' class='html-xx' data-content='58.'>Kindlund, B.; Sjoling, A.; Yakkala, C.; Adamsson, J.; Janzon, A.; Hansson, L.E.; Hermansson, M.; Janson, P.; Winqvist, O.; Lundin, S.B. CD4(+) regulatory T cells in gastric cancer mucosa are proliferating and express high levels of IL-10 but little TGF-beta. <span class='html-italic'>Gastric. Cancer</span> <b>2017</b>, <span class='html-italic'>20</span>, 116–125. [<a href="https://scholar.google.com/scholar_lookup?title=CD4(+)+regulatory+T+cells+in+gastric+cancer+mucosa+are+proliferating+and+express+high+levels+of+IL-10+but+little+TGF-beta&author=Kindlund,+B.&author=Sjoling,+A.&author=Yakkala,+C.&author=Adamsson,+J.&author=Janzon,+A.&author=Hansson,+L.E.&author=Hermansson,+M.&author=Janson,+P.&author=Winqvist,+O.&author=Lundin,+S.B.&publication_year=2017&journal=Gastric.+Cancer&volume=20&pages=116%E2%80%93125&doi=10.1007/s10120-015-0591-z" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1007/s10120-015-0591-z" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B59-cancers-13-00043' class='html-xx' data-content='59.'>Sun, M.; Wu, W.; Chen, L.; Yang, W.; Huang, X.; Ma, C.; Chen, F.; Xiao, Y.; Zhao, Y.; Yao, S.; et al. Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. <span class='html-italic'>Nat. Commun.</span> <b>2018</b>, <span class='html-italic'>9</span>, 3555. [<a href="https://scholar.google.com/scholar_lookup?title=Microbiota-derived+short-chain+fatty+acids+promote+Th1+cell+IL-10+production+to+maintain+intestinal+homeostasis&author=Sun,+M.&author=Wu,+W.&author=Chen,+L.&author=Yang,+W.&author=Huang,+X.&author=Ma,+C.&author=Chen,+F.&author=Xiao,+Y.&author=Zhao,+Y.&author=Yao,+S.&publication_year=2018&journal=Nat.+Commun.&volume=9&pages=3555&doi=10.1038/s41467-018-05901-2" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/s41467-018-05901-2" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://www.nature.com/articles/s41467-018-05901-2.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B60-cancers-13-00043' class='html-xx' data-content='60.'>Cottrez, F.; Groux, H. Regulation of TGF-beta response during T cell activation is modulated by IL-10. <span class='html-italic'>J. Immunol.</span> <b>2001</b>, <span class='html-italic'>167</span>, 773–778. [<a href="https://scholar.google.com/scholar_lookup?title=Regulation+of+TGF-beta+response+during+T+cell+activation+is+modulated+by+IL-10&author=Cottrez,+F.&author=Groux,+H.&publication_year=2001&journal=J.+Immunol.&volume=167&pages=773%E2%80%93778&doi=10.4049/jimmunol.167.2.773" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.4049/jimmunol.167.2.773" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.jimmunol.org/content/167/2/773.full.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B61-cancers-13-00043' class='html-xx' data-content='61.'>Zhao, R.; Song, Y.; Wang, Y.; Huang, Y.; Li, Z.; Cui, Y.; Yi, M.; Xia, L.; Zhuang, W.; Wu, X.; et al. PD-1/PD-L1 blockade rescue exhausted CD8+ T cells in gastrointestinal stromal tumours via the PI3K/Akt/mTOR signalling pathway. <span class='html-italic'>Cell Prolif.</span> <b>2019</b>, <span class='html-italic'>52</span>, e12571. [<a href="https://scholar.google.com/scholar_lookup?title=PD-1/PD-L1+blockade+rescue+exhausted+CD8++T+cells+in+gastrointestinal+stromal+tumours+via+the+PI3K/Akt/mTOR+signalling+pathway&author=Zhao,+R.&author=Song,+Y.&author=Wang,+Y.&author=Huang,+Y.&author=Li,+Z.&author=Cui,+Y.&author=Yi,+M.&author=Xia,+L.&author=Zhuang,+W.&author=Wu,+X.&publication_year=2019&journal=Cell+Prolif.&volume=52&pages=e12571&doi=10.1111/cpr.12571&pmid=30714229" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1111/cpr.12571" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/30714229" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cpr.12571" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B62-cancers-13-00043' class='html-xx' data-content='62.'>Cai, J.; Wang, D.; Zhang, G.; Guo, X. The Role Of PD-1/PD-L1 Axis In Treg Development And Function: Implications For Cancer Immunotherapy. <span class='html-italic'>Onco Targets Ther.</span> <b>2019</b>, <span class='html-italic'>12</span>, 8437–8445. [<a href="https://scholar.google.com/scholar_lookup?title=The+Role+Of+PD-1/PD-L1+Axis+In+Treg+Development+And+Function:+Implications+For+Cancer+Immunotherapy&author=Cai,+J.&author=Wang,+D.&author=Zhang,+G.&author=Guo,+X.&publication_year=2019&journal=Onco+Targets+Ther.&volume=12&pages=8437%E2%80%938445&doi=10.2147/OTT.S221340" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.2147/OTT.S221340" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://www.dovepress.com/getfile.php?fileID=53299" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B63-cancers-13-00043' class='html-xx' data-content='63.'>Routy, B.; Le Chatelier, E.; Derosa, L.; Duong, C.P.M.; Alou, M.T.; Daillere, R.; Fluckiger, A.; Messaoudene, M.; Rauber, C.; Roberti, M.P.; et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. <span class='html-italic'>Science</span> <b>2018</b>, <span class='html-italic'>359</span>, 91–97. [<a href="https://scholar.google.com/scholar_lookup?title=Gut+microbiome+influences+efficacy+of+PD-1-based+immunotherapy+against+epithelial+tumors&author=Routy,+B.&author=Le+Chatelier,+E.&author=Derosa,+L.&author=Duong,+C.P.M.&author=Alou,+M.T.&author=Daillere,+R.&author=Fluckiger,+A.&author=Messaoudene,+M.&author=Rauber,+C.&author=Roberti,+M.P.&publication_year=2018&journal=Science&volume=359&pages=91%E2%80%9397&doi=10.1126/science.aan3706&pmid=29097494" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1126/science.aan3706" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/29097494" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://science.sciencemag.org/content/sci/359/6371/91.full.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B64-cancers-13-00043' class='html-xx' data-content='64.'>Limeta, A.; Ji, B.; Levin, M.; Gatto, F.; Nielsen, J. Meta-analysis of the gut microbiota in predicting response to cancer immunotherapy in metastatic melanoma. <span class='html-italic'>JCI Insight</span> <b>2020</b>, <span class='html-italic'>5</span>. [<a href="https://scholar.google.com/scholar_lookup?title=Meta-analysis+of+the+gut+microbiota+in+predicting+response+to+cancer+immunotherapy+in+metastatic+melanoma&author=Limeta,+A.&author=Ji,+B.&author=Levin,+M.&author=Gatto,+F.&author=Nielsen,+J.&publication_year=2020&journal=JCI+Insight&volume=5&doi=10.1172/jci.insight.140940&pmid=33268597" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1172/jci.insight.140940" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/33268597" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B65-cancers-13-00043' class='html-xx' data-content='65.'>Cong, J.; Zhang, X. Roles of intestinal microbiota in response to cancer immunotherapy. <span class='html-italic'>Eur. J. Clin. Microbiol. Infect Dis.</span> <b>2018</b>, <span class='html-italic'>37</span>, 2235–2240. [<a href="https://scholar.google.com/scholar_lookup?title=Roles+of+intestinal+microbiota+in+response+to+cancer+immunotherapy&author=Cong,+J.&author=Zhang,+X.&publication_year=2018&journal=Eur.+J.+Clin.+Microbiol.+Infect+Dis.&volume=37&pages=2235%E2%80%932240&doi=10.1007/s10096-018-3374-8" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1007/s10096-018-3374-8" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B66-cancers-13-00043' class='html-xx' data-content='66.'>Ma, N.; Xing, C.; Xiao, H.; Wang, Y.; Wang, K.; Hou, C.; Han, G.; Chen, G.; Marrero, B.; Shen, B.; et al. C5a regulates IL-12+ DC migration to induce pathogenic Th1 and Th17 cells in sepsis. <span class='html-italic'>PLoS ONE</span> <b>2013</b>, <span class='html-italic'>8</span>, e69779. [<a href="https://scholar.google.com/scholar_lookup?title=C5a+regulates+IL-12++DC+migration+to+induce+pathogenic+Th1+and+Th17+cells+in+sepsis&author=Ma,+N.&author=Xing,+C.&author=Xiao,+H.&author=Wang,+Y.&author=Wang,+K.&author=Hou,+C.&author=Han,+G.&author=Chen,+G.&author=Marrero,+B.&author=Shen,+B.&publication_year=2013&journal=PLoS+ONE&volume=8&pages=e69779&doi=10.1371/journal.pone.0069779&pmid=23936099" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1371/journal.pone.0069779" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/23936099" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0069779&type=printable" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B67-cancers-13-00043' class='html-xx' data-content='67.'>Vetizou, M.; Pitt, J.M.; Daillere, R.; Lepage, P.; Waldschmitt, N.; Flament, C.; Rusakiewicz, S.; Routy, B.; Roberti, M.P.; Duong, C.P.; et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. <span class='html-italic'>Science</span> <b>2015</b>, <span class='html-italic'>350</span>, 1079–1084. [<a href="https://scholar.google.com/scholar_lookup?title=Anticancer+immunotherapy+by+CTLA-4+blockade+relies+on+the+gut+microbiota&author=Vetizou,+M.&author=Pitt,+J.M.&author=Daillere,+R.&author=Lepage,+P.&author=Waldschmitt,+N.&author=Flament,+C.&author=Rusakiewicz,+S.&author=Routy,+B.&author=Roberti,+M.P.&author=Duong,+C.P.&publication_year=2015&journal=Science&volume=350&pages=1079%E2%80%931084&doi=10.1126/science.aad1329&pmid=26541610" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1126/science.aad1329" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/26541610" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="http://europepmc.org/articles/pmc4721659?pdf=render" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B68-cancers-13-00043' class='html-xx' data-content='68.'>Yi, M.; Jiao, D.; Qin, S.; Chu, Q.; Li, A.; Wu, K. Manipulating Gut Microbiota Composition to Enhance the Therapeutic Effect of Cancer Immunotherapy. <span class='html-italic'>Integr. Cancer Ther.</span> <b>2019</b>, <span class='html-italic'>18</span>, 1534735419876351. [<a href="https://scholar.google.com/scholar_lookup?title=Manipulating+Gut+Microbiota+Composition+to+Enhance+the+Therapeutic+Effect+of+Cancer+Immunotherapy&author=Yi,+M.&author=Jiao,+D.&author=Qin,+S.&author=Chu,+Q.&author=Li,+A.&author=Wu,+K.&publication_year=2019&journal=Integr.+Cancer+Ther.&volume=18&pages=1534735419876351&doi=10.1177/1534735419876351&pmid=31517538" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1177/1534735419876351" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/31517538" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://journals.sagepub.com/doi/pdf/10.1177/1534735419876351" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B69-cancers-13-00043' class='html-xx' data-content='69.'>Inamura, K. Roles of microbiota in response to cancer immunotherapy. <span class='html-italic'>Semin. Cancer Biol.</span> <b>2020</b>, <span class='html-italic'>65</span>, 164–175. [<a href="https://scholar.google.com/scholar_lookup?title=Roles+of+microbiota+in+response+to+cancer+immunotherapy&author=Inamura,+K.&publication_year=2020&journal=Semin.+Cancer+Biol.&volume=65&pages=164%E2%80%93175&doi=10.1016/j.semcancer.2019.12.026&pmid=31911189" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.semcancer.2019.12.026" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/31911189" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B70-cancers-13-00043' class='html-xx' data-content='70.'>Sun, J.Y.; Yin, T.L.; Zhou, J.; Xu, J.; Lu, X.J. Gut microbiome and cancer immunotherapy. <span class='html-italic'>J. Cell Physiol.</span> <b>2020</b>, <span class='html-italic'>235</span>, 4082–4088. [<a href="https://scholar.google.com/scholar_lookup?title=Gut+microbiome+and+cancer+immunotherapy&author=Sun,+J.Y.&author=Yin,+T.L.&author=Zhou,+J.&author=Xu,+J.&author=Lu,+X.J.&publication_year=2020&journal=J.+Cell+Physiol.&volume=235&pages=4082%E2%80%934088&doi=10.1002/jcp.29359" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/jcp.29359" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B71-cancers-13-00043' class='html-xx' data-content='71.'>Soldati, L.; Di Renzo, L.; Jirillo, E.; Ascierto, P.A.; Marincola, F.M.; De Lorenzo, A. The influence of diet on anti-cancer immune responsiveness. <span class='html-italic'>J. Transl. Med.</span> <b>2018</b>, <span class='html-italic'>16</span>, 75. [<a href="https://scholar.google.com/scholar_lookup?title=The+influence+of+diet+on+anti-cancer+immune+responsiveness&author=Soldati,+L.&author=Di+Renzo,+L.&author=Jirillo,+E.&author=Ascierto,+P.A.&author=Marincola,+F.M.&author=De+Lorenzo,+A.&publication_year=2018&journal=J.+Transl.+Med.&volume=16&pages=75&doi=10.1186/s12967-018-1448-0" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1186/s12967-018-1448-0" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B72-cancers-13-00043' class='html-xx' data-content='72.'>Inamura, K. Gut microbiota contributes towards immunomodulation against cancer: New frontiers in precision cancer therapeutics. <span class='html-italic'>Semin. Cancer Biol.</span> <b>2020</b>. [<a href="https://scholar.google.com/scholar_lookup?title=Gut+microbiota+contributes+towards+immunomodulation+against+cancer:+New+frontiers+in+precision+cancer+therapeutics&author=Inamura,+K.&publication_year=2020&journal=Semin.+Cancer+Biol.&doi=10.1016/j.semcancer.2020.06.006&pmid=32580023" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.semcancer.2020.06.006" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/32580023" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B73-cancers-13-00043' class='html-xx' data-content='73.'>Helmink, B.A.; Khan, M.A.W.; Hermann, A.; Gopalakrishnan, V.; Wargo, J.A. The microbiome, cancer, and cancer therapy. <span class='html-italic'>Nat. Med.</span> <b>2019</b>, <span class='html-italic'>25</span>, 377–388. [<a href="https://scholar.google.com/scholar_lookup?title=The+microbiome,+cancer,+and+cancer+therapy&author=Helmink,+B.A.&author=Khan,+M.A.W.&author=Hermann,+A.&author=Gopalakrishnan,+V.&author=Wargo,+J.A.&publication_year=2019&journal=Nat.+Med.&volume=25&pages=377%E2%80%93388&doi=10.1038/s41591-019-0377-7&pmid=30842679" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/s41591-019-0377-7" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/30842679" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B74-cancers-13-00043' class='html-xx' data-content='74.'>Spakowicz, D.; Hoyd, R.; Muniak, M.; Husain, M.; Bassett, J.S.; Wang, L.; Tinoco, G.; Patel, S.H.; Burkart, J.; Miah, A.; et al. Inferring the role of the microbiome on survival in patients treated with immune checkpoint inhibitors: Causal modeling, timing, and classes of concomitant medications. <span class='html-italic'>BMC Cancer</span> <b>2020</b>, <span class='html-italic'>20</span>, 383. [<a href="https://scholar.google.com/scholar_lookup?title=Inferring+the+role+of+the+microbiome+on+survival+in+patients+treated+with+immune+checkpoint+inhibitors:+Causal+modeling,+timing,+and+classes+of+concomitant+medications&author=Spakowicz,+D.&author=Hoyd,+R.&author=Muniak,+M.&author=Husain,+M.&author=Bassett,+J.S.&author=Wang,+L.&author=Tinoco,+G.&author=Patel,+S.H.&author=Burkart,+J.&author=Miah,+A.&publication_year=2020&journal=BMC+Cancer&volume=20&pages=383&doi=10.1186/s12885-020-06882-6&pmid=32375706" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1186/s12885-020-06882-6" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/32375706" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B75-cancers-13-00043' class='html-xx' data-content='75.'>Rossi, G.; Pezzuto, A.; Sini, C.; Tuzi, A.; Citarella, F.; McCusker, M.G.; Nigro, O.; Tanda, E.; Russo, A. Concomitant medications during immune checkpoint blockage in cancer patients: Novel insights in this emerging clinical scenario. <span class='html-italic'>Crit. Rev. Oncol. Hematol.</span> <b>2019</b>, <span class='html-italic'>142</span>, 26–34. [<a href="https://scholar.google.com/scholar_lookup?title=Concomitant+medications+during+immune+checkpoint+blockage+in+cancer+patients:+Novel+insights+in+this+emerging+clinical+scenario&author=Rossi,+G.&author=Pezzuto,+A.&author=Sini,+C.&author=Tuzi,+A.&author=Citarella,+F.&author=McCusker,+M.G.&author=Nigro,+O.&author=Tanda,+E.&author=Russo,+A.&publication_year=2019&journal=Crit.+Rev.+Oncol.+Hematol.&volume=142&pages=26%E2%80%9334&doi=10.1016/j.critrevonc.2019.07.005" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.critrevonc.2019.07.005" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B76-cancers-13-00043' class='html-xx' data-content='76.'>Bruno, G.; Zaccari, P.; Rocco, G.; Scalese, G.; Panetta, C.; Porowska, B.; Pontone, S.; Severi, C. Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified. <span class='html-italic'>World J. Gastroenterol.</span> <b>2019</b>, <span class='html-italic'>25</span>, 2706–2719. [<a href="https://scholar.google.com/scholar_lookup?title=Proton+pump+inhibitors+and+dysbiosis:+Current+knowledge+and+aspects+to+be+clarified&author=Bruno,+G.&author=Zaccari,+P.&author=Rocco,+G.&author=Scalese,+G.&author=Panetta,+C.&author=Porowska,+B.&author=Pontone,+S.&author=Severi,+C.&publication_year=2019&journal=World+J.+Gastroenterol.&volume=25&pages=2706%E2%80%932719&doi=10.3748/wjg.v25.i22.2706" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3748/wjg.v25.i22.2706" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B77-cancers-13-00043' class='html-xx' data-content='77.'>Verdura, S.; Cuyas, E.; Martin-Castillo, B.; Menendez, J.A. Metformin as an archetype immuno-metabolic adjuvant for cancer immunotherapy. <span class='html-italic'>Oncoimmunology</span> <b>2019</b>, <span class='html-italic'>8</span>, e1633235. [<a href="https://scholar.google.com/scholar_lookup?title=Metformin+as+an+archetype+immuno-metabolic+adjuvant+for+cancer+immunotherapy&author=Verdura,+S.&author=Cuyas,+E.&author=Martin-Castillo,+B.&author=Menendez,+J.A.&publication_year=2019&journal=Oncoimmunology&volume=8&pages=e1633235&doi=10.1080/2162402X.2019.1633235" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1080/2162402X.2019.1633235" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B78-cancers-13-00043' class='html-xx' data-content='78.'>Chalabi, M.; Cardona, A.; Nagarkar, D.R.; Dhawahir Scala, A.; Gandara, D.R.; Rittmeyer, A.; Albert, M.L.; Powles, T.; Kok, M.; Herrera, F.G. Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung cancer receiving antibiotics and proton pump inhibitors: Pooled post hoc analyses of the OAK and POPLAR trials. <span class='html-italic'>Ann. Oncol.</span> <b>2020</b>, <span class='html-italic'>31</span>, 525–531. [<a href="https://scholar.google.com/scholar_lookup?title=Efficacy+of+chemotherapy+and+atezolizumab+in+patients+with+non-small-cell+lung+cancer+receiving+antibiotics+and+proton+pump+inhibitors:+Pooled+post+hoc+analyses+of+the+OAK+and+POPLAR+trials&author=Chalabi,+M.&author=Cardona,+A.&author=Nagarkar,+D.R.&author=Dhawahir+Scala,+A.&author=Gandara,+D.R.&author=Rittmeyer,+A.&author=Albert,+M.L.&author=Powles,+T.&author=Kok,+M.&author=Herrera,+F.G.&publication_year=2020&journal=Ann.+Oncol.&volume=31&pages=525%E2%80%93531&doi=10.1016/j.annonc.2020.01.006" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.annonc.2020.01.006" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B79-cancers-13-00043' class='html-xx' data-content='79.'>Hopkins, A.M.; Kichenadasse, G.; Karapetis, C.S.; Rowland, A.; Sorich, M.J. Concomitant Proton Pump Inhibitor Use and Survival in Urothelial Carcinoma Treated with Atezolizumab. <span class='html-italic'>Clin. Cancer Res.</span> <b>2020</b>, <span class='html-italic'>26</span>, 5487–5493. [<a href="https://scholar.google.com/scholar_lookup?title=Concomitant+Proton+Pump+Inhibitor+Use+and+Survival+in+Urothelial+Carcinoma+Treated+with+Atezolizumab&author=Hopkins,+A.M.&author=Kichenadasse,+G.&author=Karapetis,+C.S.&author=Rowland,+A.&author=Sorich,+M.J.&publication_year=2020&journal=Clin.+Cancer+Res.&volume=26&pages=5487%E2%80%935493&doi=10.1158/1078-0432.CCR-20-1876" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1158/1078-0432.CCR-20-1876" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B80-cancers-13-00043' class='html-xx' data-content='80.'>Robertson, D.J.; Larsson, H.; Friis, S.; Pedersen, L.; Baron, J.A.; Sorensen, H.T. Proton pump inhibitor use and risk of colorectal cancer: A population-based, case-control study. <span class='html-italic'>Gastroenterology</span> <b>2007</b>, <span class='html-italic'>133</span>, 755–760. [<a href="https://scholar.google.com/scholar_lookup?title=Proton+pump+inhibitor+use+and+risk+of+colorectal+cancer:+A+population-based,+case-control+study&author=Robertson,+D.J.&author=Larsson,+H.&author=Friis,+S.&author=Pedersen,+L.&author=Baron,+J.A.&author=Sorensen,+H.T.&publication_year=2007&journal=Gastroenterology&volume=133&pages=755%E2%80%93760&doi=10.1053/j.gastro.2007.06.014" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1053/j.gastro.2007.06.014" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B81-cancers-13-00043' class='html-xx' data-content='81.'>Yang, Y.X.; Hennessy, S.; Propert, K.; Hwang, W.T.; Sedarat, A.; Lewis, J.D. Chronic proton pump inhibitor therapy and the risk of colorectal cancer. <span class='html-italic'>Gastroenterology</span> <b>2007</b>, <span class='html-italic'>133</span>, 748–754. [<a href="https://scholar.google.com/scholar_lookup?title=Chronic+proton+pump+inhibitor+therapy+and+the+risk+of+colorectal+cancer&author=Yang,+Y.X.&author=Hennessy,+S.&author=Propert,+K.&author=Hwang,+W.T.&author=Sedarat,+A.&author=Lewis,+J.D.&publication_year=2007&journal=Gastroenterology&volume=133&pages=748%E2%80%93754&doi=10.1053/j.gastro.2007.06.022&pmid=17678926" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1053/j.gastro.2007.06.022" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/17678926" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B82-cancers-13-00043' class='html-xx' data-content='82.'>Lei, W.Y.; Wang, J.H.; Yi, C.H.; Liu, T.T.; Hung, J.S.; Wong, M.W.; Bair, M.J.; Vaezi, M.F.; Orr, W.C.; Chen, C.L. Association between use of proton pump inhibitors and colorectal cancer: A nationwide population-based study. <span class='html-italic'>Clin. Res. Hepatol. Gastroenterol.</span> <b>2020</b>. [<a href="https://scholar.google.com/scholar_lookup?title=Association+between+use+of+proton+pump+inhibitors+and+colorectal+cancer:+A+nationwide+population-based+study&author=Lei,+W.Y.&author=Wang,+J.H.&author=Yi,+C.H.&author=Liu,+T.T.&author=Hung,+J.S.&author=Wong,+M.W.&author=Bair,+M.J.&author=Vaezi,+M.F.&author=Orr,+W.C.&author=Chen,+C.L.&publication_year=2020&journal=Clin.+Res.+Hepatol.+Gastroenterol.&doi=10.1016/j.clinre.2020.02.017&pmid=32224118" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.clinre.2020.02.017" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/32224118" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B83-cancers-13-00043' class='html-xx' data-content='83.'>Yang, Y.S.H.; Chang, H.W.; Lin, I.H.; Chien, L.N.; Wu, M.J.; Liu, Y.R.; Chu, P.G.; Xie, G.; Dong, F.; Jia, W.; et al. Long-term Proton Pump Inhibitor Administration Caused Physiological and Microbiota Changes in Rats. <span class='html-italic'>Sci. Rep.</span> <b>2020</b>, <span class='html-italic'>10</span>, 866. [<a href="https://scholar.google.com/scholar_lookup?title=Long-term+Proton+Pump+Inhibitor+Administration+Caused+Physiological+and+Microbiota+Changes+in+Rats&author=Yang,+Y.S.H.&author=Chang,+H.W.&author=Lin,+I.H.&author=Chien,+L.N.&author=Wu,+M.J.&author=Liu,+Y.R.&author=Chu,+P.G.&author=Xie,+G.&author=Dong,+F.&author=Jia,+W.&publication_year=2020&journal=Sci.+Rep.&volume=10&pages=866&doi=10.1038/s41598-020-57612-8&pmid=31964941" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/s41598-020-57612-8" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/31964941" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B84-cancers-13-00043' class='html-xx' data-content='84.'>Imhann, F.; Bonder, M.J.; Vich Vila, A.; Fu, J.; Mujagic, Z.; Vork, L.; Tigchelaar, E.F.; Jankipersadsing, S.A.; Cenit, M.C.; Harmsen, H.J.; et al. Proton pump inhibitors affect the gut microbiome. <span class='html-italic'>Gut</span> <b>2016</b>, <span class='html-italic'>65</span>, 740–748. [<a href="https://scholar.google.com/scholar_lookup?title=Proton+pump+inhibitors+affect+the+gut+microbiome&author=Imhann,+F.&author=Bonder,+M.J.&author=Vich+Vila,+A.&author=Fu,+J.&author=Mujagic,+Z.&author=Vork,+L.&author=Tigchelaar,+E.F.&author=Jankipersadsing,+S.A.&author=Cenit,+M.C.&author=Harmsen,+H.J.&publication_year=2016&journal=Gut&volume=65&pages=740%E2%80%93748&doi=10.1136/gutjnl-2015-310376" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1136/gutjnl-2015-310376" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://gut.bmj.com/content/gutjnl/65/5/740.full.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B85-cancers-13-00043' class='html-xx' data-content='85.'>Jackson, M.A.; Goodrich, J.K.; Maxan, M.E.; Freedberg, D.E.; Abrams, J.A.; Poole, A.C.; Sutter, J.L.; Welter, D.; Ley, R.E.; Bell, J.T.; et al. Proton pump inhibitors alter the composition of the gut microbiota. <span class='html-italic'>Gut</span> <b>2016</b>, <span class='html-italic'>65</span>, 749–756. [<a href="https://scholar.google.com/scholar_lookup?title=Proton+pump+inhibitors+alter+the+composition+of+the+gut+microbiota&author=Jackson,+M.A.&author=Goodrich,+J.K.&author=Maxan,+M.E.&author=Freedberg,+D.E.&author=Abrams,+J.A.&author=Poole,+A.C.&author=Sutter,+J.L.&author=Welter,+D.&author=Ley,+R.E.&author=Bell,+J.T.&publication_year=2016&journal=Gut&volume=65&pages=749%E2%80%93756&doi=10.1136/gutjnl-2015-310861" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1136/gutjnl-2015-310861" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B86-cancers-13-00043' class='html-xx' data-content='86.'>Sun, L.; Xie, C.; Wang, G.; Wu, Y.; Wu, Q.; Wang, X.; Liu, J.; Deng, Y.; Xia, J.; Chen, B.; et al. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. <span class='html-italic'>Nat. Med.</span> <b>2018</b>, <span class='html-italic'>24</span>, 1919–1929. [<a href="https://scholar.google.com/scholar_lookup?title=Gut+microbiota+and+intestinal+FXR+mediate+the+clinical+benefits+of+metformin&author=Sun,+L.&author=Xie,+C.&author=Wang,+G.&author=Wu,+Y.&author=Wu,+Q.&author=Wang,+X.&author=Liu,+J.&author=Deng,+Y.&author=Xia,+J.&author=Chen,+B.&publication_year=2018&journal=Nat.+Med.&volume=24&pages=1919%E2%80%931929&doi=10.1038/s41591-018-0222-4" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/s41591-018-0222-4" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B87-cancers-13-00043' class='html-xx' data-content='87.'>Ma, W.; Chen, J.; Meng, Y.; Yang, J.; Cui, Q.; Zhou, Y. Metformin Alters Gut Microbiota of Healthy Mice: Implication for Its Potential Role in Gut Microbiota Homeostasis. <span class='html-italic'>Front. Microbiol.</span> <b>2018</b>, <span class='html-italic'>9</span>, 1336. [<a href="https://scholar.google.com/scholar_lookup?title=Metformin+Alters+Gut+Microbiota+of+Healthy+Mice:+Implication+for+Its+Potential+Role+in+Gut+Microbiota+Homeostasis&author=Ma,+W.&author=Chen,+J.&author=Meng,+Y.&author=Yang,+J.&author=Cui,+Q.&author=Zhou,+Y.&publication_year=2018&journal=Front.+Microbiol.&volume=9&pages=1336&doi=10.3389/fmicb.2018.01336" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3389/fmicb.2018.01336" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://www.frontiersin.org/articles/10.3389/fmicb.2018.01336/pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B88-cancers-13-00043' class='html-xx' data-content='88.'>Kyriachenko, Y.; Falalyeyeva, T.; Korotkyi, O.; Molochek, N.; Kobyliak, N. Crosstalk between gut microbiota and antidiabetic drug action. <span class='html-italic'>World J. Diabetes</span> <b>2019</b>, <span class='html-italic'>10</span>, 154–168. [<a href="https://scholar.google.com/scholar_lookup?title=Crosstalk+between+gut+microbiota+and+antidiabetic+drug+action&author=Kyriachenko,+Y.&author=Falalyeyeva,+T.&author=Korotkyi,+O.&author=Molochek,+N.&author=Kobyliak,+N.&publication_year=2019&journal=World+J.+Diabetes&volume=10&pages=154%E2%80%93168&doi=10.4239/wjd.v10.i3.154" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.4239/wjd.v10.i3.154" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B89-cancers-13-00043' class='html-xx' data-content='89.'>Wu, H.; Esteve, E.; Tremaroli, V.; Khan, M.T.; Caesar, R.; Manneras-Holm, L.; Stahlman, M.; Olsson, L.M.; Serino, M.; Planas-Felix, M.; et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. <span class='html-italic'>Nat. Med.</span> <b>2017</b>, <span class='html-italic'>23</span>, 850–858. [<a href="https://scholar.google.com/scholar_lookup?title=Metformin+alters+the+gut+microbiome+of+individuals+with+treatment-naive+type+2+diabetes,+contributing+to+the+therapeutic+effects+of+the+drug&author=Wu,+H.&author=Esteve,+E.&author=Tremaroli,+V.&author=Khan,+M.T.&author=Caesar,+R.&author=Manneras-Holm,+L.&author=Stahlman,+M.&author=Olsson,+L.M.&author=Serino,+M.&author=Planas-Felix,+M.&publication_year=2017&journal=Nat.+Med.&volume=23&pages=850%E2%80%93858&doi=10.1038/nm.4345" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/nm.4345" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B90-cancers-13-00043' class='html-xx' data-content='90.'>Huang, X.; Hong, X.; Wang, J.; Sun, T.; Yu, T.; Yu, Y.; Fang, J.; Xiong, H. Metformin elicits antitumour effect by modulation of the gut microbiota and rescues Fusobacterium nucleatum-induced colorectal tumourigenesis. <span class='html-italic'>EBioMedicine</span> <b>2020</b>, <span class='html-italic'>61</span>, 103037. [<a href="https://scholar.google.com/scholar_lookup?title=Metformin+elicits+antitumour+effect+by+modulation+of+the+gut+microbiota+and+rescues+Fusobacterium+nucleatum-induced+colorectal+tumourigenesis&author=Huang,+X.&author=Hong,+X.&author=Wang,+J.&author=Sun,+T.&author=Yu,+T.&author=Yu,+Y.&author=Fang,+J.&author=Xiong,+H.&publication_year=2020&journal=EBioMedicine&volume=61&pages=103037&doi=10.1016/j.ebiom.2020.103037" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.ebiom.2020.103037" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B91-cancers-13-00043' class='html-xx' data-content='91.'>Jones, G.R.; Molloy, M.P. Metformin, Microbiome and Protection Against Colorectal Cancer. <span class='html-italic'>Dig. Dis. Sci.</span> <b>2020</b>. [<a href="https://scholar.google.com/scholar_lookup?title=Metformin,+Microbiome+and+Protection+Against+Colorectal+Cancer&author=Jones,+G.R.&author=Molloy,+M.P.&publication_year=2020&journal=Dig.+Dis.+Sci.&doi=10.1007/s10620-020-06390-4&pmid=32533543" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1007/s10620-020-06390-4" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/32533543" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>]</li><li id='B92-cancers-13-00043' class='html-xx' data-content='92.'>Higurashi, T.; Hosono, K.; Takahashi, H.; Komiya, Y.; Umezawa, S.; Sakai, E.; Uchiyama, T.; Taniguchi, L.; Hata, Y.; Uchiyama, S.; et al. Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: A multicentre double-blind, placebo-controlled, randomised phase 3 trial. <span class='html-italic'>Lancet Oncol.</span> <b>2016</b>, <span class='html-italic'>17</span>, 475–483. [<a href="https://scholar.google.com/scholar_lookup?title=Metformin+for+chemoprevention+of+metachronous+colorectal+adenoma+or+polyps+in+post-polypectomy+patients+without+diabetes:+A+multicentre+double-blind,+placebo-controlled,+randomised+phase+3+trial&author=Higurashi,+T.&author=Hosono,+K.&author=Takahashi,+H.&author=Komiya,+Y.&author=Umezawa,+S.&author=Sakai,+E.&author=Uchiyama,+T.&author=Taniguchi,+L.&author=Hata,+Y.&author=Uchiyama,+S.&publication_year=2016&journal=Lancet+Oncol.&volume=17&pages=475%E2%80%93483&doi=10.1016/S1470-2045(15)00565-3" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/S1470-2045(15)00565-3" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B93-cancers-13-00043' class='html-xx' data-content='93.'>Kostic, A.D.; Chun, E.; Robertson, L.; Glickman, J.N.; Gallini, C.A.; Michaud, M.; Clancy, T.E.; Chung, D.C.; Lochhead, P.; Hold, G.L.; et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. <span class='html-italic'>Cell Host Microbe</span> <b>2013</b>, <span class='html-italic'>14</span>, 207–215. [<a href="https://scholar.google.com/scholar_lookup?title=Fusobacterium+nucleatum+potentiates+intestinal+tumorigenesis+and+modulates+the+tumor-immune+microenvironment&author=Kostic,+A.D.&author=Chun,+E.&author=Robertson,+L.&author=Glickman,+J.N.&author=Gallini,+C.A.&author=Michaud,+M.&author=Clancy,+T.E.&author=Chung,+D.C.&author=Lochhead,+P.&author=Hold,+G.L.&publication_year=2013&journal=Cell+Host+Microbe&volume=14&pages=207%E2%80%93215&doi=10.1016/j.chom.2013.07.007&pmid=23954159" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.chom.2013.07.007" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/23954159" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="http://www.cell.com/article/S1931312813002552/pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B94-cancers-13-00043' class='html-xx' data-content='94.'>Provenzale, D.; Gupta, S.; Ahnen, D.J.; Markowitz, A.J.; Chung, D.C.; Mayer, R.J.; Regenbogen, S.E.; Blanco, A.M.; Bray, T.; Cooper, G.; et al. NCCN Guidelines Insights: Colorectal Cancer Screening, Version 1.2018. <span class='html-italic'>J. Natl. Compr. Cancer Netw.</span> <b>2018</b>, <span class='html-italic'>16</span>, 939–949. [<a href="https://scholar.google.com/scholar_lookup?title=NCCN+Guidelines+Insights:+Colorectal+Cancer+Screening,+Version+1.2018&author=Provenzale,+D.&author=Gupta,+S.&author=Ahnen,+D.J.&author=Markowitz,+A.J.&author=Chung,+D.C.&author=Mayer,+R.J.&author=Regenbogen,+S.E.&author=Blanco,+A.M.&author=Bray,+T.&author=Cooper,+G.&publication_year=2018&journal=J.+Natl.+Compr.+Cancer+Netw.&volume=16&pages=939%E2%80%93949&doi=10.6004/jnccn.2018.0067" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.6004/jnccn.2018.0067" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B95-cancers-13-00043' class='html-xx' data-content='95.'>Le, D.T.; Durham, J.N.; Smith, K.N.; Wang, H.; Bartlett, B.R.; Aulakh, L.K.; Lu, S.; Kemberling, H.; Wilt, C.; Luber, B.S.; et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. <span class='html-italic'>Science</span> <b>2017</b>, <span class='html-italic'>357</span>, 409–413. [<a href="https://scholar.google.com/scholar_lookup?title=Mismatch+repair+deficiency+predicts+response+of+solid+tumors+to+PD-1+blockade&author=Le,+D.T.&author=Durham,+J.N.&author=Smith,+K.N.&author=Wang,+H.&author=Bartlett,+B.R.&author=Aulakh,+L.K.&author=Lu,+S.&author=Kemberling,+H.&author=Wilt,+C.&author=Luber,+B.S.&publication_year=2017&journal=Science&volume=357&pages=409%E2%80%93413&doi=10.1126/science.aan6733" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1126/science.aan6733" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://science.sciencemag.org/content/sci/357/6349/409.full.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B96-cancers-13-00043' class='html-xx' data-content='96.'>Coleman, O.I.; Lobner, E.M.; Bierwirth, S.; Sorbie, A.; Waldschmitt, N.; Rath, E.; Berger, E.; Lagkouvardos, I.; Clavel, T.; McCoy, K.D.; et al. Activated ATF6 Induces Intestinal Dysbiosis and Innate Immune Response to Promote Colorectal Tumorigenesis. <span class='html-italic'>Gastroenterology</span> <b>2018</b>, <span class='html-italic'>155</span>, 1539–1552. [<a href="https://scholar.google.com/scholar_lookup?title=Activated+ATF6+Induces+Intestinal+Dysbiosis+and+Innate+Immune+Response+to+Promote+Colorectal+Tumorigenesis&author=Coleman,+O.I.&author=Lobner,+E.M.&author=Bierwirth,+S.&author=Sorbie,+A.&author=Waldschmitt,+N.&author=Rath,+E.&author=Berger,+E.&author=Lagkouvardos,+I.&author=Clavel,+T.&author=McCoy,+K.D.&publication_year=2018&journal=Gastroenterology&volume=155&pages=1539%E2%80%931552&doi=10.1053/j.gastro.2018.07.028" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1053/j.gastro.2018.07.028" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.gastrojournal.org/article/S0016508518348169/pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B97-cancers-13-00043' class='html-xx' data-content='97.'>Li, S.K.H.; Martin, A. Mismatch Repair and Colon Cancer: Mechanisms and Therapies Explored. <span class='html-italic'>Trends Mol. Med.</span> <b>2016</b>, <span class='html-italic'>22</span>, 274–289. [<a href="https://scholar.google.com/scholar_lookup?title=Mismatch+Repair+and+Colon+Cancer:+Mechanisms+and+Therapies+Explored&author=Li,+S.K.H.&author=Martin,+A.&publication_year=2016&journal=Trends+Mol.+Med.&volume=22&pages=274%E2%80%93289&doi=10.1016/j.molmed.2016.02.003" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.molmed.2016.02.003" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B98-cancers-13-00043' class='html-xx' data-content='98.'>Gur, C.; Ibrahim, Y.; Isaacson, B.; Yamin, R.; Abed, J.; Gamliel, M.; Enk, J.; Bar-On, Y.; Stanietsky-Kaynan, N.; Coppenhagen-Glazer, S.; et al. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. <span class='html-italic'>Immunity</span> <b>2015</b>, <span class='html-italic'>42</span>, 344–355. [<a href="https://scholar.google.com/scholar_lookup?title=Binding+of+the+Fap2+protein+of+Fusobacterium+nucleatum+to+human+inhibitory+receptor+TIGIT+protects+tumors+from+immune+cell+attack&author=Gur,+C.&author=Ibrahim,+Y.&author=Isaacson,+B.&author=Yamin,+R.&author=Abed,+J.&author=Gamliel,+M.&author=Enk,+J.&author=Bar-On,+Y.&author=Stanietsky-Kaynan,+N.&author=Coppenhagen-Glazer,+S.&publication_year=2015&journal=Immunity&volume=42&pages=344%E2%80%93355&doi=10.1016/j.immuni.2015.01.010" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.immuni.2015.01.010" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.cell.com/article/S1074761315000369/pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B99-cancers-13-00043' class='html-xx' data-content='99.'>Mima, K.; Nishihara, R.; Qian, Z.R.; Cao, Y.; Sukawa, Y.; Nowak, J.A.; Yang, J.; Dou, R.; Masugi, Y.; Song, M.; et al. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. <span class='html-italic'>Gut</span> <b>2016</b>, <span class='html-italic'>65</span>, 1973–1980. [<a href="https://scholar.google.com/scholar_lookup?title=Fusobacterium+nucleatum+in+colorectal+carcinoma+tissue+and+patient+prognosis&author=Mima,+K.&author=Nishihara,+R.&author=Qian,+Z.R.&author=Cao,+Y.&author=Sukawa,+Y.&author=Nowak,+J.A.&author=Yang,+J.&author=Dou,+R.&author=Masugi,+Y.&author=Song,+M.&publication_year=2016&journal=Gut&volume=65&pages=1973%E2%80%931980&doi=10.1136/gutjnl-2015-310101" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1136/gutjnl-2015-310101" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://europepmc.org/articles/pmc4769120?pdf=render" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B100-cancers-13-00043' class='html-xxx' data-content='100.'>Lee, J.A.; Yoo, S.Y.; Oh, H.J.; Jeong, S.; Cho, N.Y.; Kang, G.H.; Kim, J.H. Differential immune microenvironmental features of microsatellite-unstable colorectal cancers according to Fusobacterium nucleatum status. <span class='html-italic'>Cancer Immunol. Immunother.</span> <b>2020</b>. [<a href="https://scholar.google.com/scholar_lookup?title=Differential+immune+microenvironmental+features+of+microsatellite-unstable+colorectal+cancers+according+to+Fusobacterium+nucleatum+status&author=Lee,+J.A.&author=Yoo,+S.Y.&author=Oh,+H.J.&author=Jeong,+S.&author=Cho,+N.Y.&author=Kang,+G.H.&author=Kim,+J.H.&publication_year=2020&journal=Cancer+Immunol.+Immunother.&doi=10.1007/s00262-020-02657-x" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1007/s00262-020-02657-x" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B101-cancers-13-00043' class='html-xxx' data-content='101.'>Donohoe, D.R.; Holley, D.; Collins, L.B.; Montgomery, S.A.; Whitmore, A.C.; Hillhouse, A.; Curry, K.P.; Renner, S.W.; Greenwalt, A.; Ryan, E.P.; et al. A gnotobiotic mouse model demonstrates that dietary fiber protects against colorectal tumorigenesis in a microbiota- and butyrate-dependent manner. <span class='html-italic'>Cancer Discov.</span> <b>2014</b>, <span class='html-italic'>4</span>, 1387–1397. [<a href="https://scholar.google.com/scholar_lookup?title=A+gnotobiotic+mouse+model+demonstrates+that+dietary+fiber+protects+against+colorectal+tumorigenesis+in+a+microbiota-+and+butyrate-dependent+manner&author=Donohoe,+D.R.&author=Holley,+D.&author=Collins,+L.B.&author=Montgomery,+S.A.&author=Whitmore,+A.C.&author=Hillhouse,+A.&author=Curry,+K.P.&author=Renner,+S.W.&author=Greenwalt,+A.&author=Ryan,+E.P.&publication_year=2014&journal=Cancer+Discov.&volume=4&pages=1387%E2%80%931397&doi=10.1158/2159-8290.CD-14-0501&pmid=25266735" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1158/2159-8290.CD-14-0501" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/25266735" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="https://cancerdiscovery.aacrjournals.org/content/candisc/4/12/1387.full.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B102-cancers-13-00043' class='html-xxx' data-content='102.'>Belcheva, A.; Irrazabal, T.; Robertson, S.J.; Streutker, C.; Maughan, H.; Rubino, S.; Moriyama, E.H.; Copeland, J.K.; Surendra, A.; Kumar, S.; et al. Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells. <span class='html-italic'>Cell</span> <b>2014</b>, <span class='html-italic'>158</span>, 288–299. [<a href="https://scholar.google.com/scholar_lookup?title=Gut+microbial+metabolism+drives+transformation+of+MSH2-deficient+colon+epithelial+cells&author=Belcheva,+A.&author=Irrazabal,+T.&author=Robertson,+S.J.&author=Streutker,+C.&author=Maughan,+H.&author=Rubino,+S.&author=Moriyama,+E.H.&author=Copeland,+J.K.&author=Surendra,+A.&author=Kumar,+S.&publication_year=2014&journal=Cell&volume=158&pages=288%E2%80%93299&doi=10.1016/j.cell.2014.04.051&pmid=25036629" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.cell.2014.04.051" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/25036629" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="http://www.cell.com/article/S0092867414007363/pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B103-cancers-13-00043' class='html-xxx' data-content='103.'>Xiao, T.; Wu, S.; Yan, C.; Zhao, C.; Jin, H.; Yan, N.; Xu, J.; Wu, Y.; Li, C.; Shao, Q.; et al. Butyrate upregulates the TLR4 expression and the phosphorylation of MAPKs and NK-kappaB in colon cancer cell in vitro. <span class='html-italic'>Oncol. Lett.</span> <b>2018</b>, <span class='html-italic'>16</span>, 4439–4447. [<a href="https://scholar.google.com/scholar_lookup?title=Butyrate+upregulates+the+TLR4+expression+and+the+phosphorylation+of+MAPKs+and+NK-kappaB+in+colon+cancer+cell+in+vitro&author=Xiao,+T.&author=Wu,+S.&author=Yan,+C.&author=Zhao,+C.&author=Jin,+H.&author=Yan,+N.&author=Xu,+J.&author=Wu,+Y.&author=Li,+C.&author=Shao,+Q.&publication_year=2018&journal=Oncol.+Lett.&volume=16&pages=4439%E2%80%934447&doi=10.3892/ol.2018.9201&pmid=30214578" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.3892/ol.2018.9201" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/30214578" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="http://www.spandidos-publications.com/10.3892/ol.2018.9201/download" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B104-cancers-13-00043' class='html-xxx' data-content='104.'>Ciorba, M.A.; Bettonville, E.E.; McDonald, K.G.; Metz, R.; Prendergast, G.C.; Newberry, R.D.; Stenson, W.F. Induction of IDO-1 by immunostimulatory DNA limits severity of experimental colitis. <span class='html-italic'>J. Immunol.</span> <b>2010</b>, <span class='html-italic'>184</span>, 3907–3916. [<a href="https://scholar.google.com/scholar_lookup?title=Induction+of+IDO-1+by+immunostimulatory+DNA+limits+severity+of+experimental+colitis&author=Ciorba,+M.A.&author=Bettonville,+E.E.&author=McDonald,+K.G.&author=Metz,+R.&author=Prendergast,+G.C.&author=Newberry,+R.D.&author=Stenson,+W.F.&publication_year=2010&journal=J.+Immunol.&volume=184&pages=3907%E2%80%933916&doi=10.4049/jimmunol.0900291" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.4049/jimmunol.0900291" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B105-cancers-13-00043' class='html-xxx' data-content='105.'>Sommariva, M.; De Cecco, L.; De Cesare, M.; Sfondrini, L.; Menard, S.; Melani, C.; Delia, D.; Zaffaroni, N.; Pratesi, G.; Uva, V.; et al. TLR9 agonists oppositely modulate DNA repair genes in tumor versus immune cells and enhance chemotherapy effects. <span class='html-italic'>Cancer Res.</span> <b>2011</b>, <span class='html-italic'>71</span>, 6382–6390. [<a href="https://scholar.google.com/scholar_lookup?title=TLR9+agonists+oppositely+modulate+DNA+repair+genes+in+tumor+versus+immune+cells+and+enhance+chemotherapy+effects&author=Sommariva,+M.&author=De+Cecco,+L.&author=De+Cesare,+M.&author=Sfondrini,+L.&author=Menard,+S.&author=Melani,+C.&author=Delia,+D.&author=Zaffaroni,+N.&author=Pratesi,+G.&author=Uva,+V.&publication_year=2011&journal=Cancer+Res.&volume=71&pages=6382%E2%80%936390&doi=10.1158/0008-5472.CAN-11-1285" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1158/0008-5472.CAN-11-1285" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://cancerres.aacrjournals.org/content/71/20/6382.full.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B106-cancers-13-00043' class='html-xxx' data-content='106.'>He, Y.W.; Wang, H.S.; Zeng, J.; Fang, X.; Chen, H.Y.; Du, J.; Yang, X.Y. Sodium butyrate inhibits interferon-gamma induced indoleamine 2,3-dioxygenase expression via STAT1 in nasopharyngeal carcinoma cells. <span class='html-italic'>Life Sci.</span> <b>2013</b>, <span class='html-italic'>93</span>, 509–515. [<a href="https://scholar.google.com/scholar_lookup?title=Sodium+butyrate+inhibits+interferon-gamma+induced+indoleamine+2,3-dioxygenase+expression+via+STAT1+in+nasopharyngeal+carcinoma+cells&author=He,+Y.W.&author=Wang,+H.S.&author=Zeng,+J.&author=Fang,+X.&author=Chen,+H.Y.&author=Du,+J.&author=Yang,+X.Y.&publication_year=2013&journal=Life+Sci.&volume=93&pages=509%E2%80%93515&doi=10.1016/j.lfs.2013.07.028" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.lfs.2013.07.028" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B107-cancers-13-00043' class='html-xxx' data-content='107.'>Jiang, G.M.; He, Y.W.; Fang, R.; Zhang, G.; Zeng, J.; Yi, Y.M.; Zhang, S.; Bu, X.Z.; Cai, S.H.; Du, J. Sodium butyrate down-regulation of indoleamine 2, 3-dioxygenase at the transcriptional and post-transcriptional levels. <span class='html-italic'>Int. J. Biochem. Cell Biol.</span> <b>2010</b>, <span class='html-italic'>42</span>, 1840–1846. [<a href="https://scholar.google.com/scholar_lookup?title=Sodium+butyrate+down-regulation+of+indoleamine+2,+3-dioxygenase+at+the+transcriptional+and+post-transcriptional+levels&author=Jiang,+G.M.&author=He,+Y.W.&author=Fang,+R.&author=Zhang,+G.&author=Zeng,+J.&author=Yi,+Y.M.&author=Zhang,+S.&author=Bu,+X.Z.&author=Cai,+S.H.&author=Du,+J.&publication_year=2010&journal=Int.+J.+Biochem.+Cell+Biol.&volume=42&pages=1840%E2%80%931846&doi=10.1016/j.biocel.2010.07.020" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.biocel.2010.07.020" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B108-cancers-13-00043' class='html-xxx' data-content='108.'>Phan, T.; Nguyen, V.H.; D’Alincourt, M.S.; Manuel, E.R.; Kaltcheva, T.; Tsai, W.; Blazar, B.R.; Diamond, D.J.; Melstrom, L.G. Salmonella-mediated therapy targeting indoleamine 2, 3-dioxygenase 1 (IDO) activates innate immunity and mitigates colorectal cancer growth. <span class='html-italic'>Cancer Gene Ther.</span> <b>2020</b>, <span class='html-italic'>27</span>, 235–245. [<a href="https://scholar.google.com/scholar_lookup?title=Salmonella-mediated+therapy+targeting+indoleamine+2,+3-dioxygenase+1+(IDO)+activates+innate+immunity+and+mitigates+colorectal+cancer+growth&author=Phan,+T.&author=Nguyen,+V.H.&author=D%E2%80%99Alincourt,+M.S.&author=Manuel,+E.R.&author=Kaltcheva,+T.&author=Tsai,+W.&author=Blazar,+B.R.&author=Diamond,+D.J.&author=Melstrom,+L.G.&publication_year=2020&journal=Cancer+Gene+Ther.&volume=27&pages=235%E2%80%93245&doi=10.1038/s41417-019-0089-7" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/s41417-019-0089-7" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B109-cancers-13-00043' class='html-xxx' data-content='109.'>Iida, N.; Dzutsev, A.; Stewart, C.A.; Smith, L.; Bouladoux, N.; Weingarten, R.A.; Molina, D.A.; Salcedo, R.; Back, T.; Cramer, S.; et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. <span class='html-italic'>Science</span> <b>2013</b>, <span class='html-italic'>342</span>, 967–970. [<a href="https://scholar.google.com/scholar_lookup?title=Commensal+bacteria+control+cancer+response+to+therapy+by+modulating+the+tumor+microenvironment&author=Iida,+N.&author=Dzutsev,+A.&author=Stewart,+C.A.&author=Smith,+L.&author=Bouladoux,+N.&author=Weingarten,+R.A.&author=Molina,+D.A.&author=Salcedo,+R.&author=Back,+T.&author=Cramer,+S.&publication_year=2013&journal=Science&volume=342&pages=967%E2%80%93970&doi=10.1126/science.1240527" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1126/science.1240527" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B110-cancers-13-00043' class='html-xxx' data-content='110.'>Tanoue, T.; Morita, S.; Plichta, D.R.; Skelly, A.N.; Suda, W.; Sugiura, Y.; Narushima, S.; Vlamakis, H.; Motoo, I.; Sugita, K.; et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. <span class='html-italic'>Nature</span> <b>2019</b>, <span class='html-italic'>565</span>, 600–605. [<a href="https://scholar.google.com/scholar_lookup?title=A+defined+commensal+consortium+elicits+CD8+T+cells+and+anti-cancer+immunity&author=Tanoue,+T.&author=Morita,+S.&author=Plichta,+D.R.&author=Skelly,+A.N.&author=Suda,+W.&author=Sugiura,+Y.&author=Narushima,+S.&author=Vlamakis,+H.&author=Motoo,+I.&author=Sugita,+K.&publication_year=2019&journal=Nature&volume=565&pages=600%E2%80%93605&doi=10.1038/s41586-019-0878-z" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/s41586-019-0878-z" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B111-cancers-13-00043' class='html-xxx' data-content='111.'>Viaud, S.; Saccheri, F.; Mignot, G.; Yamazaki, T.; Daillere, R.; Hannani, D.; Enot, D.P.; Pfirschke, C.; Engblom, C.; Pittet, M.J.; et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. <span class='html-italic'>Science</span> <b>2013</b>, <span class='html-italic'>342</span>, 971–976. [<a href="https://scholar.google.com/scholar_lookup?title=The+intestinal+microbiota+modulates+the+anticancer+immune+effects+of+cyclophosphamide&author=Viaud,+S.&author=Saccheri,+F.&author=Mignot,+G.&author=Yamazaki,+T.&author=Daillere,+R.&author=Hannani,+D.&author=Enot,+D.P.&author=Pfirschke,+C.&author=Engblom,+C.&author=Pittet,+M.J.&publication_year=2013&journal=Science&volume=342&pages=971%E2%80%93976&doi=10.1126/science.1240537&pmid=24264990" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1126/science.1240537" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://www.ncbi.nlm.nih.gov/pubmed/24264990" class='cross-ref' data-typ='pmid' target='_blank' rel='noopener noreferrer'>PubMed</a>] [<a href="http://europepmc.org/articles/pmc4048947?pdf=render" target='_blank' rel="noopener noreferrer">Green Version</a>]</li></ol></section><section id='Tables' type='display-objects'><div class="html-table-wrap" id="cancers-13-00043-t001"> <div class="html-table_wrap_td" > <div class="html-tablepopup html-tablepopup-link" data-counterslinkmanual = "https://www.mdpi.com/2072-6694/13/1/43/display" href='#table_body_display_cancers-13-00043-t001'> <img alt="Table" data-lsrc="https://www.mdpi.com/img/table.png" /> <a class="html-expand html-tablepopup" data-counterslinkmanual = "https://www.mdpi.com/2072-6694/13/1/43/display" href="#table_body_display_cancers-13-00043-t001"></a> </div> </div> <div class="html-table_wrap_discription"> <b>Table 1.</b> Bacterial species associated with enhancement of immunotherapy in solid tumors. </div> </div> <div class="html-table_show mfp-hide " id ="table_body_display_cancers-13-00043-t001" > <div class="html-caption" ><b>Table 1.</b> Bacterial species associated with enhancement of immunotherapy in solid tumors.</div> <table > <thead ><tr ><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Tumor </th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Beneficial Microbiota </th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Immune Response</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Immunotherapy</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Reference</th></tr></thead><tbody ><tr ><td align='center' valign='middle' class='html-align-center' >Melanoma</td><td align='center' valign='middle' class='html-align-center' ><span class='html-italic'>Bifidobacterium</span> spp.</td><td align='center' valign='middle' class='html-align-center' >Increase of dendritic cells function and enhancement of CD8+ T cells priming</td><td align='center' valign='middle' class='html-align-center' >anti-PD-L1</td><td align='center' valign='middle' class='html-align-center' >[<a href="#B7-cancers-13-00043" class="html-bibr">7</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >NSCLC, Renal cell or urothelial carcinoma</td><td align='center' valign='middle' class='html-align-center' ><span class='html-italic'>A. muciniphila</span></td><td align='center' valign='middle' class='html-align-center' >CD4+, CD8+ T cells memory towards <span class='html-italic'>A. mucinipilla</span></td><td align='center' valign='middle' class='html-align-center' >anti-PD-1/anti-PD-L1</td><td align='center' valign='middle' class='html-align-center' >[<a href="#B8-cancers-13-00043" class="html-bibr">8</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >Melanoma</td><td align='center' valign='middle' class='html-align-center' ><span class='html-italic'>F. prausnitzii</span>, <span class='html-italic'>B. thetaiotamicron</span>, <span class='html-italic'>H. filiformis</span> and <span class='html-italic'>B. caccae</span></td><td align='center' valign='middle' class='html-align-center' >CD8+ T cells</td><td align='center' valign='middle' class='html-align-center' >anti-PD-1/anti-CTLA-4 or combination</td><td align='center' valign='middle' class='html-align-center' >[<a href="#B9-cancers-13-00043" class="html-bibr">9</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >Melanoma</td><td align='center' valign='middle' class='html-align-center' ><span class='html-italic'>F. prausnitzii</span>, <span class='html-italic'>R. bromii</span>, <span class='html-italic'>P. pasteri</span>, <span class='html-italic'>C. hungati</span> and <span class='html-italic'>P. faecium</span></td><td align='center' valign='middle' class='html-align-center' >Increased antigen presentation, elevation of CD4+ and CD8+ T cells</td><td align='center' valign='middle' class='html-align-center' >anti-PD-1</td><td align='center' valign='middle' class='html-align-center' >[<a href="#B10-cancers-13-00043" class="html-bibr">10</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >Melanoma</td><td align='center' valign='middle' class='html-align-center' ><span class='html-italic'>F. prausnitzii</span> L2-6, <span class='html-italic'>G. formicilitis</span> ATCC27749, butyrate- producing bacteria SS2-1, <span class='html-italic'>Ruminococcus</span>, <span class='html-italic'>Lachnospiraceae</span>, <span class='html-italic'>Clostridium</span> XIVa and <span class='html-italic'>Blautia</span> spp.</td><td align='center' valign='middle' class='html-align-center' >Low Tregs in peripheral blood, increase in CD4+ cells and serum CD25</td><td align='center' valign='middle' class='html-align-center' >anti-CTLA-4</td><td align='center' valign='middle' class='html-align-center' >[<a href="#B12-cancers-13-00043" class="html-bibr">12</a>]</td></tr><tr ><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Melanoma</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' ><span class='html-italic'>Bacteroides</span> spp.</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Activation of Th cells, mobilization of CD11b+ DC to lamina propria</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >anti-CTLA-4</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >[<a href="#B26-cancers-13-00043" class="html-bibr">26</a>]</td></tr></tbody> </table> </div><div class="html-table-wrap" id="cancers-13-00043-t002"> <div class="html-table_wrap_td" > <div class="html-tablepopup html-tablepopup-link" data-counterslinkmanual = "https://www.mdpi.com/2072-6694/13/1/43/display" href='#table_body_display_cancers-13-00043-t002'> <img alt="Table" data-lsrc="https://www.mdpi.com/img/table.png" /> <a class="html-expand html-tablepopup" data-counterslinkmanual = "https://www.mdpi.com/2072-6694/13/1/43/display" href="#table_body_display_cancers-13-00043-t002"></a> </div> </div> <div class="html-table_wrap_discription"> <b>Table 2.</b> Interference of gut microbiota with immune response in CRC. </div> </div> <div class="html-table_show mfp-hide " id ="table_body_display_cancers-13-00043-t002" > <div class="html-caption" ><b>Table 2.</b> Interference of gut microbiota with immune response in CRC.</div> <table > <thead ><tr ><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Gut Microbiota Component/Agent Influencing Microbiota</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Correlation with CRC and/or Immunotherapy</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Immune Reaction </th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Reference</th></tr></thead><tbody ><tr ><td align='center' valign='middle' class='html-align-center' >Dysbiotic microbiota due to ATF6 activation</td><td align='center' valign='middle' class='html-align-center' >Tumorigenesis</td><td align='center' valign='middle' class='html-align-center' >MyD88/TRIF- dependent activation </td><td align='center' valign='middle' class='html-align-center' >[<a href="#B96-cancers-13-00043" class="html-bibr">96</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' ><span class='html-italic'>Fusobacterium nucleatum</span></td><td align='center' valign='middle' class='html-align-center' >tumorigenesis, dMMR CRC</td><td align='center' valign='middle' class='html-align-center' >binding to TIGIT on NK and T cells</td><td align='center' valign='middle' class='html-align-center' >[<a href="#B93-cancers-13-00043" class="html-bibr">93</a>,<a href="#B97-cancers-13-00043" class="html-bibr">97</a>,<a href="#B98-cancers-13-00043" class="html-bibr">98</a>,<a href="#B99-cancers-13-00043" class="html-bibr">99</a>,<a href="#B100-cancers-13-00043" class="html-bibr">100</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' ><span class='html-italic'>Bacteroides</span> spp. and <span class='html-italic'>Faecalibacterium</span> sp.</td><td align='center' valign='middle' class='html-align-center' >immunosurveillance </td><td align='center' valign='middle' class='html-align-center' >Raising of Tregs and M1 TAMs</td><td align='center' valign='middle' class='html-align-center' >[<a href="#B13-cancers-13-00043" class="html-bibr">13</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >Butyrate producing bacteria</td><td align='center' valign='middle' class='html-align-center' >dMMR CRC mice models: suspends tumor growth, reserves microbioal homeostasis</td><td align='center' valign='middle' class='html-align-center' >upregulation of TLR4, phosphorylation of MAPKs and NF-κΒ</td><td align='center' valign='middle' class='html-align-center' >[<a href="#B102-cancers-13-00043" class="html-bibr">102</a>,<a href="#B103-cancers-13-00043" class="html-bibr">103</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >Lysates of <span class='html-italic'>Lactobacillus acidophilus</span> </td><td align='center' valign='middle' class='html-align-center' >improvement of antitumor immune response</td><td align='center' valign='middle' class='html-align-center' >Increase of CD8+ Tcells, effector memory T cells, decrease of Tregs and M2 TAMs</td><td align='center' valign='middle' class='html-align-center' >[<a href="#B16-cancers-13-00043" class="html-bibr">16</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >shRNA targeting IDO delivered via attenuated <span class='html-italic'>Salmonella typhimurium</span> </td><td align='center' valign='middle' class='html-align-center' >supresses tumor growth</td><td align='center' valign='middle' class='html-align-center' >Increase of intratumoral neutrophil concetration </td><td align='center' valign='middle' class='html-align-center' >[<a href="#B108-cancers-13-00043" class="html-bibr">108</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >Bacteroidales S24-7 in Control group, <span class='html-italic'>A. municiphila</span> in Vanc group, <span class='html-italic'>Bacteroides</span> in Coli group</td><td align='center' valign='middle' class='html-align-center' >enhace antitumor antiPD-1 activity in MMR-proficient CRC</td><td align='center' valign='middle' class='html-align-center' >changes in the expression of INF-γ and IL-2 in tumor microenvironment</td><td align='center' valign='middle' class='html-align-center' >[<a href="#B17-cancers-13-00043" class="html-bibr">17</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' ><span class='html-italic'>Alistipes shahii</span> and <span class='html-italic'>Ruminococcus</span> spp.</td><td align='center' valign='middle' class='html-align-center' >Enhacement of antitumor response of immunotherapy</td><td align='center' valign='middle' class='html-align-center' >TLR4, TNF production</td><td align='center' valign='middle' class='html-align-center' >[<a href="#B109-cancers-13-00043" class="html-bibr">109</a>]</td></tr><tr ><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' ><span class='html-italic'>Ruthenibacterium lactatiformans</span>, <span class='html-italic'>Eubacterium limosum</span>, <span class='html-italic'>F. ulcerans</span>, <span class='html-italic'>Phascolarctobacterium succinatutens</span>, <span class='html-italic'>Bacteroides uniformis</span>, <span class='html-italic'>B. dorei</span>, <span class='html-italic'>Paraprevotella xylaniphila</span>, <span class='html-italic'>Parabacteroides johnsonii</span>, <span class='html-italic'>P. gordonii</span> and <span class='html-italic'>Alistipes senegalensis</span> </td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >enhancement of antitumor ICI’s effect</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Induce interferon-γ+ CD8 T cells</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >[<a href="#B110-cancers-13-00043" class="html-bibr">110</a>]</td></tr></tbody> </table> </div></section><section class='html-fn_group'><table><tr id=''><td></td><td><div class='html-p'><b>Publisher’s Note:</b> MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.</div></td></tr></table></section> <section id="html-copyright"><br>© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<a href='http://creativecommons.org/licenses/by/4.0/' target='_blank' rel="noopener noreferrer" >http://creativecommons.org/licenses/by/4.0/</a>).</section> </div> </div> <div class="additional-content"> <h2><a name="cite"></a>Share and Cite</h2> <div class="social-media-links" style="text-align: left;"> <a href="/cdn-cgi/l/email-protection#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" title="Email"> <i class="fa fa-envelope-square" style="font-size: 30px;"></i> </a> <a href="https://twitter.com/intent/tweet?text=Immunotherapy+in+Solid+Tumors+and+Gut+Microbiota%3A+The+Correlation%E2%80%94A+Special+Reference+to+Colorectal+Cancer&hashtags=mdpicancers&url=https%3A%2F%2Fwww.mdpi.com%2F936826&via=Cancers_MDPI" onclick="windowOpen(this.href,600,800); return false" target="_blank" rel="noopener noreferrer"> <i class="fa fa-twitter-x-square" style="font-size: 30px;"></i> </a> <a href=" http://www.linkedin.com/shareArticle?mini=true&url=https%3A%2F%2Fwww.mdpi.com%2F936826&title=Immunotherapy%20in%20Solid%20Tumors%20and%20Gut%20Microbiota%3A%20The%20Correlation%E2%80%94A%20Special%20Reference%20to%20Colorectal%20Cancer%26source%3Dhttps%3A%2F%2Fwww.mdpi.com%26summary%3DOver%20the%20last%20few%20years%2C%20immunotherapy%20has%20been%20considered%20as%20a%20key%20player%20in%20the%20treatment%20of%20solid%20tumors.%20Immune%20checkpoint%20inhibitors%20%28ICIs%29%20have%20become%20the%20breakthrough%20treatment%2C%20with%20prolonged%20responses%20and%20improved%20survival%20results.%20ICIs%20use%20%5B...%5D" onclick="windowOpen(this.href,600,800); return false" title="LinkedIn" target="_blank" rel="noopener noreferrer"> <i class="fa fa-linkedin-square" style="font-size: 30px;"></i> </a> <a href="https://www.facebook.com/sharer.php?u=https://www.mdpi.com/936826" title="facebook" target="_blank" rel="noopener noreferrer"> <i class="fa fa-facebook-square" style="font-size: 30px;"></i> </a> <a href="javascript:void(0);" title="Wechat" data-reveal-id="weixin-share-modal"> <i class="fa fa-weixin-square" style="font-size: 26px;"></i> </a> <a href="http://www.reddit.com/submit?url=https://www.mdpi.com/936826" title="Reddit" target="_blank" rel="noopener noreferrer"> <i class="fa fa-reddit-square" style="font-size: 30px;"></i> </a> <a href="http://www.mendeley.com/import/?url=https://www.mdpi.com/936826" title="Mendeley" target="_blank" rel="noopener noreferrer"> <i class="fa fa-mendeley-square" style="font-size: 30px;"></i> </a> </div> <div class="in-tab" style="padding-top: 0px!important; margin-top: 15px;"> <div><b>MDPI and ACS Style</b></div> <p> Koulouridi, A.; Messaritakis, I.; Gouvas, N.; Tsiaoussis, J.; Souglakos, J. Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer. <em>Cancers</em> <b>2021</b>, <em>13</em>, 43. https://doi.org/10.3390/cancers13010043 </p> <div style="display: block"> <b>AMA Style</b><br> <p> Koulouridi A, Messaritakis I, Gouvas N, Tsiaoussis J, Souglakos J. Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer. <em>Cancers</em>. 2021; 13(1):43. https://doi.org/10.3390/cancers13010043 </p> <b>Chicago/Turabian Style</b><br> <p> Koulouridi, Asimina, Ippokratis Messaritakis, Nikolaos Gouvas, John Tsiaoussis, and John Souglakos. 2021. "Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer" <em>Cancers</em> 13, no. 1: 43. https://doi.org/10.3390/cancers13010043 </p> <b>APA Style</b><br> <p> Koulouridi, A., Messaritakis, I., Gouvas, N., Tsiaoussis, J., & Souglakos, J. (2021). Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer. <em>Cancers</em>, <em>13</em>(1), 43. https://doi.org/10.3390/cancers13010043 </p> </div> </div> <div class="info-box no-margin"> Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details <a target="_blank" href="https://www.mdpi.com/about/announcements/784">here</a>. </div> <h2><a name="metrics"></a>Article Metrics</h2> <div class="row"> <div class="small-12 columns"> <div id="loaded_cite_count" style="display:none">No</div> <div id="framed_div_cited_count" class="in-tab" style="display: none; overflow: auto;"></div> <div id="loaded" style="display:none">No</div> <div id="framed_div" class="in-tab" style="display: none; margin-top: 10px;"></div> </div> <div class="small-12 columns"> <div id="article_stats_div" style="display: none; margin-bottom: 1em;"> <h3>Article Access Statistics</h3> <div id="article_stats_swf" ></div> For more information on the journal statistics, click <a href="/journal/cancers/stats">here</a>. <div class="info-box"> Multiple requests from the same IP address are counted as one view. </div> </div> </div> </div> </div> </div> </article> </div> </div></div> <div class="webpymol-controls webpymol-controls-template" style="margin-top: 10px; display: none;"> <a class="bzoom">Zoom</a> <span style="display: inline-block; margin-left: 5px; margin-right: 5px;">|</span> <a class="borient"> Orient </a> <span style="display: inline-block; margin-left: 5px; margin-right: 5px;">|</span> <a class="blines"> As Lines </a> <span style="display: inline-block; margin-left: 5px; margin-right: 5px;">|</span> <a class="bsticks"> As Sticks </a> <span style="display: inline-block; margin-left: 5px; margin-right: 5px;">|</span> <a class="bcartoon"> As Cartoon </a> <span style="display: inline-block; margin-left: 5px; margin-right: 5px;">|</span> <a class="bsurface"> As Surface </a> <span style="display: inline-block; margin-left: 5px; margin-right: 5px;">|</span> <a class="bprevscene">Previous Scene</a> <span style="display: inline-block; margin-left: 5px; margin-right: 5px;">|</span> <a class="bnextscene">Next Scene</a> </div> <div id="scifeed-modal" class="reveal-modal reveal-modal-new" data-reveal aria-labelledby="modalTitle" aria-hidden="true" role="dialog"> </div> <div id="recommended-articles-modal" class="reveal-modal reveal-modal-new" data-reveal aria-labelledby="modalTitle" aria-hidden="true" role="dialog"> </div> <div id="author-biographies-modal" class="reveal-modal reveal-modal-new" data-reveal aria-labelledby="modalTitle" aria-hidden="true" role="dialog"> </div> <div id="cite-modal" class="reveal-modal reveal-modal-new" data-reveal aria-labelledby="Captcha" aria-hidden="true" role="dialog"> <div class="row"> <div class="small-12 columns"> <h2 style="margin: 0;">Cite</h2> </div> <div class="small-12 columns">  <form style="margin:0; padding:0; display:inline;" name="export-bibtex" method="POST" action="/export"> <input type="hidden" name="articles_ids[]" value="468413"> <input type="hidden" name="export_format_top" value="bibtex"> <input type="hidden" name="export_submit_top" value=""> </form>  <form style="margin:0; padding:0; display:inline;" name="export-endnote" method="POST" action="/export"> <input type="hidden" name="articles_ids[]" value="468413"> <input type="hidden" name="export_format_top" value="endnote_no_abstract"> <input type="hidden" name="export_submit_top" value=""> </form>  <form style="margin:0; padding:0; display:inline;" name="export-ris" method="POST" action="/export"> <input type="hidden" name="articles_ids[]" value="468413"> <input type="hidden" name="export_format_top" value="ris"> <input type="hidden" name="export_submit_top" value=""> </form> <div> Export citation file: <a href="javascript:window.document.forms['export-bibtex'].submit()">BibTeX</a> | <a href="javascript:window.document.forms['export-endnote'].submit()">EndNote</a> | <a href="javascript:window.document.forms['export-ris'].submit()">RIS</a> </div> </div> <div class="small-12 columns"> <div class="in-tab"> <div><b>MDPI and ACS Style</b></div> <p> Koulouridi, A.; Messaritakis, I.; Gouvas, N.; Tsiaoussis, J.; Souglakos, J. Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer. <em>Cancers</em> <b>2021</b>, <em>13</em>, 43. https://doi.org/10.3390/cancers13010043 </p> <div style="display: block"> <b>AMA Style</b><br> <p> Koulouridi A, Messaritakis I, Gouvas N, Tsiaoussis J, Souglakos J. Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer. <em>Cancers</em>. 2021; 13(1):43. https://doi.org/10.3390/cancers13010043 </p> <b>Chicago/Turabian Style</b><br> <p> Koulouridi, Asimina, Ippokratis Messaritakis, Nikolaos Gouvas, John Tsiaoussis, and John Souglakos. 2021. "Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer" <em>Cancers</em> 13, no. 1: 43. https://doi.org/10.3390/cancers13010043 </p> <b>APA Style</b><br> <p> Koulouridi, A., Messaritakis, I., Gouvas, N., Tsiaoussis, J., & Souglakos, J. (2021). Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer. <em>Cancers</em>, <em>13</em>(1), 43. https://doi.org/10.3390/cancers13010043 </p> </div> </div> <div class="info-box no-margin"> Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details <a target="_blank" href="https://www.mdpi.com/about/announcements/784">here</a>. </div> </div> </div> <a class="close-reveal-modal" aria-label="Close"> <i class="material-icons">clear</i> </a> </div> </div> </div> </div> </div> </section> <div id="footer"> <div class="journal-info"> <span> <em><a class="Var_JournalInfo" href="/journal/cancers">Cancers</a></em>, EISSN 2072-6694, Published by MDPI </span> <div class="large-right"> <span> <a href="/rss/journal/cancers" class="rss-link">RSS</a> </span> <span> <a href="/journal/cancers/toc-alert">Content Alert</a> </span> </div> </div> <div class="row full-width footer-links" data-equalizer="footer" data-equalizer-mq="small"> <div class="large-2 large-push-4 medium-3 small-6 columns" data-equalizer-watch="footer"> <h3> Further Information </h3> <a href="/apc"> Article Processing Charges </a> <a href="/about/payment"> Pay an Invoice </a> <a href="/openaccess"> Open Access Policy </a> <a href="/about/contact"> Contact MDPI </a> <a href="https://careers.mdpi.com" target="_blank" rel="noopener noreferrer"> Jobs at MDPI </a> </div> <div class="large-2 large-push-4 medium-3 small-6 columns" data-equalizer-watch="footer"> <h3> Guidelines </h3> <a href="/authors"> For Authors </a> <a href="/reviewers"> For Reviewers </a> <a href="/editors"> For Editors </a> <a href="/librarians"> For Librarians </a> <a href="/publishing_services"> For Publishers </a> <a href="/societies"> For Societies </a> <a href="/conference_organizers"> For Conference Organizers </a> </div> <div class="large-2 large-push-4 medium-3 small-6 columns"> <h3> MDPI Initiatives </h3> <a href="https://sciforum.net" target="_blank" rel="noopener noreferrer"> Sciforum </a> <a href="https://www.mdpi.com/books" target="_blank" rel="noopener noreferrer"> MDPI Books </a> <a href="https://www.preprints.org" target="_blank" rel="noopener noreferrer"> Preprints.org </a> <a href="https://www.scilit.com" target="_blank" rel="noopener noreferrer"> Scilit </a> <a href="https://sciprofiles.com?utm_source=mpdi.com&utm_medium=bottom_menu&utm_campaign=initiative" target="_blank" rel="noopener noreferrer"> SciProfiles </a> <a href="https://encyclopedia.pub" target="_blank" rel="noopener noreferrer"> Encyclopedia </a> <a href="https://jams.pub" target="_blank" rel="noopener noreferrer"> JAMS </a> <a href="/about/proceedings"> Proceedings Series </a> </div> <div class="large-2 large-push-4 medium-3 small-6 right-border-large-without columns UA_FooterFollowMDPI"> <h3> Follow MDPI </h3> <a href="https://www.linkedin.com/company/mdpi" target="_blank" rel="noopener noreferrer"> LinkedIn </a> <a href="https://www.facebook.com/MDPIOpenAccessPublishing" target="_blank" rel="noopener noreferrer"> Facebook </a> <a href="https://twitter.com/MDPIOpenAccess" target="_blank" rel="noopener noreferrer"> Twitter </a> </div> <div id="footer-subscribe" class="large-4 large-pull-8 medium-12 small-12 left-border-large columns"> <div class="footer-subscribe__container"> <img class="show-for-large-up" src="https://pub.mdpi-res.com/img/design/mdpi-pub-logo-white-small.png?71d18e5f805839ab?1739771134" alt="MDPI" title="MDPI Open Access Journals" style="height: 50px; margin-bottom: 10px;"> <form id="newsletter" method="POST" action="/subscribe"> <p> Subscribe to receive issue release notifications and newsletters from MDPI journals </p> <select multiple id="newsletter-journal" class="foundation-select" name="journals[]"> <option value="acoustics">Acoustics</option> <option value="amh">Acta Microbiologica Hellenica</option> <option value="actuators">Actuators</option> <option value="adhesives">Adhesives</option> <option value="admsci">Administrative Sciences</option> <option value="adolescents">Adolescents</option> <option value="arm">Advances in Respiratory Medicine</option> <option value="aerobiology">Aerobiology</option> <option value="aerospace">Aerospace</option> <option value="agriculture">Agriculture</option> <option value="agriengineering">AgriEngineering</option> <option value="agrochemicals">Agrochemicals</option> <option value="agronomy">Agronomy</option> <option value="ai">AI</option> <option value="aisens">AI Sensors</option> <option value="air">Air</option> <option value="algorithms">Algorithms</option> <option value="allergies">Allergies</option> <option value="alloys">Alloys</option> <option value="analytica">Analytica</option> <option value="analytics">Analytics</option> <option value="anatomia">Anatomia</option> <option value="anesthres">Anesthesia Research</option> <option value="animals">Animals</option> <option value="antibiotics">Antibiotics</option> <option value="antibodies">Antibodies</option> <option value="antioxidants">Antioxidants</option> <option value="applbiosci">Applied Biosciences</option> <option value="applmech">Applied Mechanics</option> <option value="applmicrobiol">Applied Microbiology</option> <option value="applnano">Applied Nano</option> <option value="applsci">Applied Sciences</option> <option value="asi">Applied System Innovation</option> <option value="appliedchem">AppliedChem</option> <option value="appliedmath">AppliedMath</option> <option value="aquacj">Aquaculture Journal</option> <option value="architecture">Architecture</option> <option value="arthropoda">Arthropoda</option> <option value="arts">Arts</option> <option value="astronomy">Astronomy</option> <option value="atmosphere">Atmosphere</option> <option value="atoms">Atoms</option> <option value="audiolres">Audiology Research</option> <option value="automation">Automation</option> <option value="axioms">Axioms</option> <option value="bacteria">Bacteria</option> <option value="batteries">Batteries</option> <option value="behavsci">Behavioral Sciences</option> <option value="beverages">Beverages</option> <option value="BDCC">Big Data and Cognitive Computing</option> <option value="biochem">BioChem</option> <option value="bioengineering">Bioengineering</option> <option value="biologics">Biologics</option> <option value="biology">Biology</option> <option value="blsf">Biology and Life Sciences Forum</option> <option value="biomass">Biomass</option> <option value="biomechanics">Biomechanics</option> <option value="biomed">BioMed</option> <option value="biomedicines">Biomedicines</option> <option value="biomedinformatics">BioMedInformatics</option> <option value="biomimetics">Biomimetics</option> <option value="biomolecules">Biomolecules</option> <option value="biophysica">Biophysica</option> <option value="biosensors">Biosensors</option> <option value="biosphere">Biosphere</option> <option value="biotech">BioTech</option> <option value="birds">Birds</option> <option value="blockchains">Blockchains</option> <option value="brainsci">Brain Sciences</option> <option value="buildings">Buildings</option> <option value="businesses">Businesses</option> <option value="carbon">C</option> <option value="cancers">Cancers</option> <option value="cardiogenetics">Cardiogenetics</option> <option value="catalysts">Catalysts</option> <option value="cells">Cells</option> <option value="ceramics">Ceramics</option> <option value="challenges">Challenges</option> <option value="ChemEngineering">ChemEngineering</option> <option value="chemistry">Chemistry</option> <option value="chemproc">Chemistry Proceedings</option> <option value="chemosensors">Chemosensors</option> <option value="children">Children</option> <option value="chips">Chips</option> <option value="civileng">CivilEng</option> <option value="cleantechnol">Clean Technologies</option> <option value="climate">Climate</option> <option value="ctn">Clinical and Translational Neuroscience</option> <option value="clinbioenerg">Clinical Bioenergetics</option> <option value="clinpract">Clinics and Practice</option> <option value="clockssleep">Clocks & Sleep</option> <option value="coasts">Coasts</option> <option value="coatings">Coatings</option> <option value="colloids">Colloids and Interfaces</option> <option value="colorants">Colorants</option> <option value="commodities">Commodities</option> <option value="complications">Complications</option> <option value="compounds">Compounds</option> <option value="computation">Computation</option> <option value="csmf">Computer Sciences & Mathematics Forum</option> <option value="computers">Computers</option> <option value="condensedmatter">Condensed Matter</option> <option value="conservation">Conservation</option> <option value="constrmater">Construction Materials</option> <option value="cmd">Corrosion and Materials Degradation</option> <option value="cosmetics">Cosmetics</option> <option value="covid">COVID</option> <option value="cmtr">Craniomaxillofacial Trauma & Reconstruction</option> <option value="crops">Crops</option> <option value="cryo">Cryo</option> <option value="cryptography">Cryptography</option> <option value="crystals">Crystals</option> <option value="cimb">Current Issues in Molecular Biology</option> <option value="curroncol">Current Oncology</option> <option value="dairy">Dairy</option> <option value="data">Data</option> <option value="dentistry">Dentistry Journal</option> <option value="dermato">Dermato</option> <option value="dermatopathology">Dermatopathology</option> <option value="designs">Designs</option> <option value="diabetology">Diabetology</option> <option value="diagnostics">Diagnostics</option> <option value="dietetics">Dietetics</option> <option value="digital">Digital</option> <option value="disabilities">Disabilities</option> <option value="diseases">Diseases</option> <option value="diversity">Diversity</option> <option value="dna">DNA</option> <option value="drones">Drones</option> <option value="ddc">Drugs and Drug Candidates</option> <option value="dynamics">Dynamics</option> <option value="earth">Earth</option> <option value="ecologies">Ecologies</option> <option value="econometrics">Econometrics</option> <option value="economies">Economies</option> <option value="education">Education Sciences</option> <option value="electricity">Electricity</option> <option value="electrochem">Electrochem</option> <option value="electronicmat">Electronic Materials</option> <option value="electronics">Electronics</option> <option value="ecm">Emergency Care and Medicine</option> <option value="encyclopedia">Encyclopedia</option> <option value="endocrines">Endocrines</option> <option value="energies">Energies</option> <option value="esa">Energy Storage and Applications</option> <option value="eng">Eng</option> <option value="engproc">Engineering Proceedings</option> <option value="entropy">Entropy</option> <option value="eesp">Environmental and Earth Sciences Proceedings</option> <option value="environments">Environments</option> <option value="epidemiologia">Epidemiologia</option> <option value="epigenomes">Epigenomes</option> <option value="ebj">European Burn Journal</option> <option value="ejihpe">European Journal of Investigation in Health, Psychology and Education</option> <option value="fermentation">Fermentation</option> <option value="fibers">Fibers</option> <option value="fintech">FinTech</option> <option value="fire">Fire</option> <option value="fishes">Fishes</option> <option value="fluids">Fluids</option> <option value="foods">Foods</option> <option value="forecasting">Forecasting</option> <option value="forensicsci">Forensic Sciences</option> <option value="forests">Forests</option> <option value="fossstud">Fossil Studies</option> <option value="foundations">Foundations</option> <option value="fractalfract">Fractal and Fractional</option> <option value="fuels">Fuels</option> <option value="future">Future</option> <option value="futureinternet">Future Internet</option> <option value="futurepharmacol">Future Pharmacology</option> <option value="futuretransp">Future Transportation</option> <option value="galaxies">Galaxies</option> <option value="games">Games</option> <option value="gases">Gases</option> <option value="gastroent">Gastroenterology Insights</option> <option value="gastrointestdisord">Gastrointestinal Disorders</option> <option value="gastronomy">Gastronomy</option> <option value="gels">Gels</option> <option value="genealogy">Genealogy</option> <option value="genes">Genes</option> <option value="geographies">Geographies</option> <option value="geohazards">GeoHazards</option> <option value="geomatics">Geomatics</option> <option value="geometry">Geometry</option> <option value="geosciences">Geosciences</option> <option value="geotechnics">Geotechnics</option> <option value="geriatrics">Geriatrics</option> <option value="glacies">Glacies</option> <option value="gucdd">Gout, Urate, and Crystal Deposition Disease</option> <option value="grasses">Grasses</option> <option value="greenhealth">Green Health</option> <option value="hardware">Hardware</option> <option value="healthcare">Healthcare</option> <option value="hearts">Hearts</option> <option value="hemato">Hemato</option> <option value="hematolrep">Hematology Reports</option> <option value="heritage">Heritage</option> <option value="histories">Histories</option> <option value="horticulturae">Horticulturae</option> <option value="hospitals">Hospitals</option> <option value="humanities">Humanities</option> <option value="humans">Humans</option> <option value="hydrobiology">Hydrobiology</option> <option value="hydrogen">Hydrogen</option> <option value="hydrology">Hydrology</option> <option value="hygiene">Hygiene</option> <option value="immuno">Immuno</option> <option value="idr">Infectious Disease Reports</option> <option value="informatics">Informatics</option> <option value="information">Information</option> <option value="infrastructures">Infrastructures</option> <option value="inorganics">Inorganics</option> <option value="insects">Insects</option> <option value="instruments">Instruments</option> <option value="iic">Intelligent Infrastructure and Construction</option> <option value="ijerph">International Journal of Environmental Research and Public Health</option> <option value="ijfs">International Journal of Financial Studies</option> <option value="ijms">International Journal of Molecular Sciences</option> <option value="IJNS">International Journal of Neonatal Screening</option> <option value="ijom">International Journal of Orofacial Myology and Myofunctional Therapy</option> <option value="ijpb">International Journal of Plant Biology</option> <option value="ijt">International Journal of Topology</option> <option value="ijtm">International Journal of Translational Medicine</option> <option value="ijtpp">International Journal of Turbomachinery, Propulsion and Power</option> <option value="ime">International Medical Education</option> <option value="inventions">Inventions</option> <option value="IoT">IoT</option> <option value="ijgi">ISPRS International Journal of Geo-Information</option> <option value="J">J</option> <option value="jal">Journal of Ageing and Longevity</option> <option value="jcdd">Journal of Cardiovascular Development and Disease</option> <option value="jcto">Journal of Clinical & Translational Ophthalmology</option> <option value="jcm">Journal of Clinical Medicine</option> <option value="jcs">Journal of Composites Science</option> <option value="jcp">Journal of Cybersecurity and Privacy</option> <option value="jdad">Journal of Dementia and Alzheimer's Disease</option> <option value="jdb">Journal of Developmental Biology</option> <option value="jeta">Journal of Experimental and Theoretical Analyses</option> <option value="jemr">Journal of Eye Movement Research</option> <option value="jfb">Journal of Functional Biomaterials</option> <option value="jfmk">Journal of Functional Morphology and Kinesiology</option> <option value="jof">Journal of Fungi</option> <option value="jimaging">Journal of Imaging</option> <option value="jintelligence">Journal of Intelligence</option> <option value="jlpea">Journal of Low Power Electronics and Applications</option> <option value="jmmp">Journal of Manufacturing and Materials Processing</option> <option value="jmse">Journal of Marine Science and Engineering</option> <option value="jmahp">Journal of Market Access & Health Policy</option> <option value="jmms">Journal of Mind and Medical Sciences</option> <option value="jmp">Journal of Molecular Pathology</option> <option value="jnt">Journal of Nanotheranostics</option> <option value="jne">Journal of Nuclear Engineering</option> <option value="ohbm">Journal of Otorhinolaryngology, Hearing and Balance Medicine</option> <option value="jop">Journal of Parks</option> <option value="jpm">Journal of Personalized Medicine</option> <option value="jpbi">Journal of Pharmaceutical and BioTech Industry</option> <option value="jor">Journal of Respiration</option> <option value="jrfm">Journal of Risk and Financial Management</option> <option value="jsan">Journal of Sensor and Actuator Networks</option> <option value="joma">Journal of the Oman Medical Association</option> <option value="jtaer">Journal of Theoretical and Applied Electronic Commerce Research</option> <option value="jvd">Journal of Vascular Diseases</option> <option value="jox">Journal of Xenobiotics</option> <option value="jzbg">Journal of Zoological and Botanical Gardens</option> <option value="journalmedia">Journalism and Media</option> <option value="kidneydial">Kidney and Dialysis</option> <option value="kinasesphosphatases">Kinases and Phosphatases</option> <option value="knowledge">Knowledge</option> <option value="labmed">LabMed</option> <option value="laboratories">Laboratories</option> <option value="land">Land</option> <option value="languages">Languages</option> <option value="laws">Laws</option> <option value="life">Life</option> <option value="limnolrev">Limnological Review</option> <option value="lipidology">Lipidology</option> <option value="liquids">Liquids</option> <option value="literature">Literature</option> <option value="livers">Livers</option> <option value="logics">Logics</option> <option value="logistics">Logistics</option> <option value="lubricants">Lubricants</option> <option value="lymphatics">Lymphatics</option> <option value="make">Machine Learning and Knowledge Extraction</option> <option value="machines">Machines</option> <option value="macromol">Macromol</option> <option value="magnetism">Magnetism</option> <option value="magnetochemistry">Magnetochemistry</option> <option value="marinedrugs">Marine Drugs</option> <option value="materials">Materials</option> <option value="materproc">Materials Proceedings</option> <option value="mca">Mathematical and Computational Applications</option> <option value="mathematics">Mathematics</option> <option value="medsci">Medical Sciences</option> <option value="msf">Medical Sciences Forum</option> <option value="medicina">Medicina</option> <option value="medicines">Medicines</option> <option value="membranes">Membranes</option> <option value="merits">Merits</option> <option value="metabolites">Metabolites</option> <option value="metals">Metals</option> <option value="meteorology">Meteorology</option> <option value="methane">Methane</option> <option value="mps">Methods and Protocols</option> <option value="metrics">Metrics</option> <option value="metrology">Metrology</option> <option value="micro">Micro</option> <option value="microbiolres">Microbiology Research</option> <option value="micromachines">Micromachines</option> <option value="microorganisms">Microorganisms</option> <option value="microplastics">Microplastics</option> <option value="microwave">Microwave</option> <option value="minerals">Minerals</option> <option value="mining">Mining</option> <option value="modelling">Modelling</option> <option value="mmphys">Modern Mathematical Physics</option> <option value="molbank">Molbank</option> <option value="molecules">Molecules</option> <option value="mti">Multimodal Technologies and Interaction</option> <option value="muscles">Muscles</option> <option value="nanoenergyadv">Nanoenergy Advances</option> <option value="nanomanufacturing">Nanomanufacturing</option> <option value="nanomaterials">Nanomaterials</option> <option value="ndt">NDT</option> <option value="network">Network</option> <option value="neuroglia">Neuroglia</option> <option value="neurolint">Neurology International</option> <option value="neurosci">NeuroSci</option> <option value="nitrogen">Nitrogen</option> <option value="ncrna">Non-Coding RNA</option> <option value="nursrep">Nursing Reports</option> <option value="nutraceuticals">Nutraceuticals</option> <option value="nutrients">Nutrients</option> <option value="obesities">Obesities</option> <option value="oceans">Oceans</option> <option value="onco">Onco</option> <option value="optics">Optics</option> <option value="oral">Oral</option> <option value="organics">Organics</option> <option value="organoids">Organoids</option> <option value="osteology">Osteology</option> <option value="oxygen">Oxygen</option> <option value="parasitologia">Parasitologia</option> <option value="particles">Particles</option> <option value="pathogens">Pathogens</option> <option value="pathophysiology">Pathophysiology</option> <option value="pediatrrep">Pediatric Reports</option> <option value="pets">Pets</option> <option value="pharmaceuticals">Pharmaceuticals</option> <option value="pharmaceutics">Pharmaceutics</option> <option value="pharmacoepidemiology">Pharmacoepidemiology</option> <option value="pharmacy">Pharmacy</option> <option value="philosophies">Philosophies</option> <option value="photochem">Photochem</option> <option value="photonics">Photonics</option> <option value="phycology">Phycology</option> <option value="physchem">Physchem</option> <option value="psf">Physical Sciences Forum</option> <option value="physics">Physics</option> <option value="physiologia">Physiologia</option> <option value="plants">Plants</option> <option value="plasma">Plasma</option> <option value="platforms">Platforms</option> <option value="pollutants">Pollutants</option> <option value="polymers">Polymers</option> <option value="polysaccharides">Polysaccharides</option> <option value="populations">Populations</option> <option value="poultry">Poultry</option> <option value="powders">Powders</option> <option value="proceedings">Proceedings</option> <option value="processes">Processes</option> <option value="prosthesis">Prosthesis</option> <option value="proteomes">Proteomes</option> <option value="psychiatryint">Psychiatry International</option> <option value="psychoactives">Psychoactives</option> <option value="psycholint">Psychology International</option> <option value="publications">Publications</option> <option value="qubs">Quantum Beam Science</option> <option value="quantumrep">Quantum Reports</option> <option value="quaternary">Quaternary</option> <option value="radiation">Radiation</option> <option value="reactions">Reactions</option> <option value="realestate">Real Estate</option> <option value="receptors">Receptors</option> <option value="recycling">Recycling</option> <option value="rsee">Regional Science and Environmental Economics</option> <option value="religions">Religions</option> <option value="remotesensing">Remote Sensing</option> <option value="reports">Reports</option> <option value="reprodmed">Reproductive Medicine</option> <option value="resources">Resources</option> <option value="rheumato">Rheumato</option> <option value="risks">Risks</option> <option value="robotics">Robotics</option> <option value="ruminants">Ruminants</option> <option value="safety">Safety</option> <option value="sci">Sci</option> <option value="scipharm">Scientia Pharmaceutica</option> <option value="sclerosis">Sclerosis</option> <option value="seeds">Seeds</option> <option value="sensors">Sensors</option> <option value="separations">Separations</option> <option value="sexes">Sexes</option> <option value="signals">Signals</option> <option value="sinusitis">Sinusitis</option> <option value="smartcities">Smart Cities</option> <option value="socsci">Social Sciences</option> <option value="siuj">Société Internationale d’Urologie Journal</option> <option value="societies">Societies</option> <option value="software">Software</option> <option value="soilsystems">Soil Systems</option> <option value="solar">Solar</option> <option value="solids">Solids</option> <option value="spectroscj">Spectroscopy Journal</option> <option value="sports">Sports</option> <option value="standards">Standards</option> <option value="stats">Stats</option> <option value="stresses">Stresses</option> <option value="surfaces">Surfaces</option> <option value="surgeries">Surgeries</option> <option value="std">Surgical Techniques Development</option> <option value="sustainability">Sustainability</option> <option value="suschem">Sustainable Chemistry</option> <option value="symmetry">Symmetry</option> <option value="synbio">SynBio</option> <option value="systems">Systems</option> <option value="targets">Targets</option> <option value="taxonomy">Taxonomy</option> <option value="technologies">Technologies</option> <option value="telecom">Telecom</option> <option value="textiles">Textiles</option> <option value="thalassrep">Thalassemia Reports</option> <option value="therapeutics">Therapeutics</option> <option value="thermo">Thermo</option> <option value="timespace">Time and Space</option> <option value="tomography">Tomography</option> <option value="tourismhosp">Tourism and Hospitality</option> <option value="toxics">Toxics</option> <option value="toxins">Toxins</option> <option value="transplantology">Transplantology</option> <option value="traumacare">Trauma Care</option> <option value="higheredu">Trends in Higher Education</option> <option value="tropicalmed">Tropical Medicine and Infectious Disease</option> <option value="universe">Universe</option> <option value="urbansci">Urban Science</option> <option value="uro">Uro</option> <option value="vaccines">Vaccines</option> <option value="vehicles">Vehicles</option> <option value="venereology">Venereology</option> <option value="vetsci">Veterinary Sciences</option> <option value="vibration">Vibration</option> <option value="virtualworlds">Virtual Worlds</option> <option value="viruses">Viruses</option> <option value="vision">Vision</option> <option value="waste">Waste</option> <option value="water">Water</option> <option value="wild">Wild</option> <option value="wind">Wind</option> <option value="women">Women</option> <option value="world">World</option> <option value="wevj">World Electric Vehicle Journal</option> <option value="youth">Youth</option> <option value="zoonoticdis">Zoonotic Diseases</option> </select> <input name="email" type="email" placeholder="Enter your email address..." required="required" /> <button class="genericCaptcha button button--dark UA_FooterNewsletterSubscribeButton" type="submit">Subscribe</button> </form> </div> </div> </div> <div id="footer-copyright"> <div class="row"> <div class="columns large-6 medium-6 small-12 text-left"> © 1996-2025 MDPI (Basel, Switzerland) unless otherwise stated </div> <div class="columns large-6 medium-6 small-12 small-text-left medium-text-right large-text-right"> <a data-dropdown="drop-view-disclaimer" aria-controls="drop-view-disclaimer" aria-expanded="false" data-options="align:top; is_hover:true; hover_timeout:2000;"> Disclaimer </a> <div id="drop-view-disclaimer" class="f-dropdown label__btn__dropdown label__btn__dropdown--wide text-left" data-dropdown-content aria-hidden="true" tabindex="-1"> Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. </div> <a href="/about/terms-and-conditions"> Terms and Conditions </a> <a href="/about/privacy"> Privacy Policy </a> </div> </div> </div> </div> <div id="cookie-notification" class="js-allow-cookies" style="display: none;"> <div class="columns large-10 medium-10 small-12"> We use cookies on our website to ensure you get the best experience.<br class="show-for-medium-up"/> Read more about our cookies <a href="/about/privacy">here</a>. </div> <div class="columns large-2 medium-2 small-12 small-only-text-left text-right"> <a class="button button--default" href="/accept_cookies">Accept</a> </div> </div> </div> <div id="main-share-modal" class="reveal-modal reveal-modal-new reveal-modal-new--small" data-reveal aria-labelledby="modalTitle" aria-hidden="true" role="dialog"> <div class="row"> <div class="small-12 columns"> <h2 style="margin: 0;">Share Link</h2> </div> <div class="small-12 columns"> <div class="social-media-links UA_ShareModalLinks" style="text-align: left;"> <a href="/cdn-cgi/l/email-protection#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" title="Email"> <i class="fa fa-envelope-square" style="font-size: 30px;"></i> </a> <a href="https://twitter.com/intent/tweet?text=Immunotherapy+in+Solid+Tumors+and+Gut+Microbiota%3A+The+Correlation%E2%80%94A+Special+Reference+to+Colorectal+Cancer&hashtags=mdpicancers&url=https%3A%2F%2Fwww.mdpi.com%2F936826&via=Cancers_MDPI" onclick="windowOpen(this.href,600,800); return false" title="Twitter" target="_blank" rel="noopener noreferrer"> <i class="fa fa-twitter-x-square" style="font-size: 30px;"></i> </a> <a href=" http://www.linkedin.com/shareArticle?mini=true&url=https%3A%2F%2Fwww.mdpi.com%2F936826&title=Immunotherapy%20in%20Solid%20Tumors%20and%20Gut%20Microbiota%3A%20The%20Correlation%E2%80%94A%20Special%20Reference%20to%20Colorectal%20Cancer%26source%3Dhttps%3A%2F%2Fwww.mdpi.com%26summary%3DOver%20the%20last%20few%20years%2C%20immunotherapy%20has%20been%20considered%20as%20a%20key%20player%20in%20the%20treatment%20of%20solid%20tumors.%20Immune%20checkpoint%20inhibitors%20%28ICIs%29%20have%20become%20the%20breakthrough%20treatment%2C%20with%20prolonged%20responses%20and%20improved%20survival%20results.%20ICIs%20use%20%5B...%5D" onclick="windowOpen(this.href,600,800); return false" title="LinkedIn" target="_blank" rel="noopener noreferrer"> <i class="fa fa-linkedin-square" style="font-size: 30px;"></i> </a> <a href="https://www.facebook.com/sharer.php?u=https://www.mdpi.com/936826" title="facebook" target="_blank" rel="noopener noreferrer"> <i class="fa fa-facebook-square" style="font-size: 30px;"></i> </a> <a href="javascript:void(0);" title="Wechat" data-reveal-id="weixin-share-modal"> <i class="fa fa-weixin-square" style="font-size: 26px;"></i> </a> <a href="http://www.reddit.com/submit?url=https://www.mdpi.com/936826" title="Reddit" target="_blank" rel="noopener noreferrer"> <i class="fa fa-reddit-square" style="font-size: 30px;"></i> </a> <a href="http://www.mendeley.com/import/?url=https://www.mdpi.com/936826" title="Mendeley" target="_blank" rel="noopener noreferrer"> <i class="fa fa-mendeley-square" style="font-size: 30px;"></i> </a> <a href="http://www.citeulike.org/posturl?url=https://www.mdpi.com/936826" title="CiteULike" target="_blank" rel="noopener noreferrer"> <i class="fa fa-citeulike-square" style="font-size: 30px;"></i> </a> </div> </div> <div class="small-9 columns"> <input id="js-clipboard-text" type="text" readonly value="https://www.mdpi.com/936826" /> </div> <div class="small-3 columns text-left"> <a class="button button--color js-clipboard-copy" data-clipboard-target="#js-clipboard-text">Copy</a> </div> </div> <a class="close-reveal-modal" aria-label="Close"> <i class="material-icons">clear</i> </a> </div> <div id="weixin-share-modal" class="reveal-modal reveal-modal-new" data-reveal aria-labelledby="weixin-share-modal-title" aria-hidden="true" role="dialog"> <div class="row"> <div class="small-12 columns"> <h2 id="weixin-share-modal-title" style="margin: 0;">Share</h2> </div> <div class="small-12 columns"> <div class="weixin-qr-code-section"> <?xml version="1.0" standalone="no"?> <!DOCTYPE svg PUBLIC "-//W3C//DTD SVG 1.1//EN" "http://www.w3.org/Graphics/SVG/1.1/DTD/svg11.dtd"> <svg width="300" height="300" version="1.1" xmlns="http://www.w3.org/2000/svg"> <desc>https://www.mdpi.com/936826</desc> <g id="elements" fill="black" stroke="none"> <rect x="0" y="0" width="12" height="12" /> <rect x="12" y="0" width="12" height="12" /> <rect x="24" y="0" width="12" height="12" /> <rect x="36" y="0" width="12" height="12" /> <rect x="48" y="0" width="12" height="12" /> <rect x="60" y="0" width="12" height="12" /> <rect x="72" y="0" width="12" height="12" /> <rect x="96" y="0" width="12" height="12" /> <rect x="108" y="0" width="12" height="12" /> <rect x="120" y="0" width="12" height="12" /> <rect x="144" y="0" width="12" height="12" /> <rect x="156" y="0" width="12" height="12" /> <rect x="168" y="0" width="12" height="12" /> <rect x="180" y="0" width="12" height="12" /> <rect x="192" y="0" width="12" height="12" /> <rect x="216" y="0" width="12" height="12" /> <rect x="228" y="0" width="12" height="12" /> <rect x="240" y="0" width="12" height="12" /> <rect x="252" y="0" width="12" height="12" /> <rect x="264" y="0" width="12" height="12" /> <rect x="276" y="0" width="12" height="12" /> <rect x="288" y="0" width="12" height="12" /> <rect x="0" y="12" width="12" height="12" /> <rect x="72" y="12" width="12" height="12" /> <rect x="96" y="12" width="12" height="12" /> <rect x="108" y="12" width="12" height="12" /> <rect x="120" y="12" width="12" height="12" /> <rect x="168" y="12" width="12" height="12" /> <rect x="216" y="12" width="12" height="12" /> <rect x="288" y="12" width="12" height="12" /> <rect x="0" y="24" width="12" height="12" /> <rect x="24" y="24" width="12" height="12" /> <rect x="36" y="24" width="12" height="12" /> <rect x="48" y="24" width="12" height="12" /> <rect x="72" y="24" width="12" height="12" /> <rect x="96" y="24" width="12" height="12" /> <rect x="120" y="24" width="12" height="12" /> <rect x="132" y="24" width="12" height="12" /> <rect x="168" y="24" width="12" height="12" /> <rect x="216" y="24" width="12" height="12" /> <rect x="240" y="24" width="12" height="12" /> <rect x="252" y="24" width="12" height="12" /> <rect x="264" y="24" width="12" height="12" /> <rect x="288" y="24" width="12" height="12" /> <rect x="0" y="36" width="12" height="12" /> <rect x="24" y="36" width="12" height="12" /> <rect x="36" y="36" width="12" height="12" /> <rect x="48" y="36" width="12" height="12" /> <rect x="72" y="36" width="12" height="12" /> <rect x="96" y="36" width="12" height="12" /> <rect x="108" y="36" width="12" height="12" /> <rect x="132" y="36" width="12" height="12" /> <rect x="156" y="36" width="12" height="12" /> <rect x="168" y="36" width="12" height="12" /> <rect x="192" y="36" width="12" height="12" /> <rect x="216" y="36" width="12" height="12" /> <rect x="240" y="36" width="12" height="12" /> <rect x="252" y="36" width="12" height="12" /> <rect x="264" y="36" width="12" height="12" /> <rect x="288" y="36" width="12" height="12" /> <rect x="0" y="48" width="12" height="12" /> <rect x="24" y="48" width="12" height="12" /> <rect x="36" y="48" width="12" height="12" /> <rect x="48" y="48" width="12" height="12" /> <rect x="72" y="48" width="12" height="12" /> <rect x="168" y="48" width="12" height="12" /> <rect x="180" y="48" width="12" height="12" /> <rect x="216" y="48" width="12" height="12" /> <rect x="240" y="48" width="12" height="12" /> <rect x="252" y="48" width="12" height="12" /> <rect x="264" y="48" width="12" height="12" /> <rect x="288" y="48" width="12" height="12" /> <rect x="0" y="60" width="12" height="12" /> <rect x="72" y="60" width="12" height="12" /> <rect x="96" y="60" width="12" height="12" /> <rect x="132" y="60" width="12" height="12" /> <rect x="144" y="60" width="12" height="12" /> <rect x="192" y="60" width="12" height="12" /> <rect x="216" y="60" width="12" height="12" /> <rect x="288" y="60" width="12" height="12" /> <rect x="0" y="72" width="12" height="12" /> <rect x="12" y="72" width="12" height="12" /> <rect x="24" y="72" width="12" height="12" /> <rect x="36" y="72" width="12" height="12" /> <rect x="48" y="72" width="12" height="12" /> <rect x="60" y="72" width="12" height="12" /> <rect x="72" y="72" width="12" height="12" /> <rect x="96" y="72" width="12" height="12" /> <rect x="120" y="72" width="12" height="12" /> <rect x="144" y="72" width="12" height="12" /> <rect x="168" y="72" width="12" height="12" /> <rect x="192" y="72" width="12" height="12" /> <rect x="216" y="72" width="12" height="12" /> <rect x="228" y="72" width="12" height="12" /> <rect x="240" y="72" width="12" height="12" /> <rect x="252" y="72" width="12" height="12" /> <rect x="264" y="72" width="12" height="12" /> <rect x="276" y="72" width="12" height="12" /> <rect x="288" y="72" width="12" height="12" /> <rect x="108" y="84" width="12" height="12" /> <rect x="144" y="84" width="12" height="12" /> <rect x="168" y="84" width="12" height="12" /> <rect x="180" y="84" width="12" height="12" /> <rect x="192" y="84" width="12" height="12" /> <rect x="0" y="96" width="12" height="12" /> <rect x="12" y="96" width="12" height="12" /> <rect x="48" y="96" width="12" height="12" /> <rect x="60" y="96" width="12" height="12" /> <rect x="72" y="96" width="12" height="12" /> <rect x="132" y="96" width="12" height="12" /> <rect x="144" y="96" width="12" height="12" /> <rect x="180" y="96" width="12" height="12" /> <rect x="228" y="96" width="12" height="12" /> <rect x="252" y="96" width="12" height="12" /> <rect x="264" y="96" width="12" height="12" /> <rect x="276" y="96" width="12" height="12" /> <rect x="288" y="96" width="12" height="12" /> <rect x="0" y="108" width="12" height="12" /> <rect x="24" y="108" width="12" height="12" /> <rect x="36" y="108" width="12" height="12" /> <rect x="48" y="108" width="12" height="12" /> <rect x="60" y="108" width="12" height="12" /> <rect x="108" y="108" width="12" height="12" /> <rect x="120" y="108" width="12" height="12" /> <rect x="144" y="108" width="12" height="12" /> <rect x="168" y="108" width="12" height="12" /> <rect x="180" y="108" width="12" height="12" /> <rect x="192" y="108" width="12" height="12" /> <rect x="204" y="108" width="12" height="12" /> <rect x="240" y="108" width="12" height="12" /> <rect x="252" y="108" width="12" height="12" /> <rect x="276" y="108" width="12" height="12" /> <rect x="0" y="120" width="12" height="12" /> <rect x="12" y="120" width="12" height="12" /> <rect x="24" y="120" width="12" height="12" /> <rect x="48" y="120" width="12" height="12" /> <rect x="60" y="120" width="12" height="12" /> <rect x="72" y="120" width="12" height="12" /> <rect x="84" y="120" width="12" height="12" /> <rect x="96" y="120" width="12" height="12" /> <rect x="132" y="120" width="12" height="12" /> <rect x="168" y="120" width="12" height="12" /> <rect x="180" y="120" width="12" height="12" /> <rect x="192" y="120" width="12" height="12" /> <rect x="228" y="120" width="12" height="12" /> <rect x="240" y="120" width="12" height="12" /> <rect x="252" y="120" width="12" height="12" /> <rect x="264" y="120" width="12" height="12" /> <rect x="12" y="132" width="12" height="12" /> <rect x="24" y="132" width="12" height="12" /> <rect x="36" y="132" width="12" height="12" /> <rect x="48" y="132" width="12" height="12" /> <rect x="84" y="132" width="12" height="12" /> <rect x="96" y="132" width="12" height="12" /> <rect x="120" y="132" width="12" height="12" /> <rect x="144" y="132" width="12" height="12" /> <rect x="168" y="132" width="12" height="12" /> <rect x="180" y="132" width="12" height="12" /> <rect x="192" y="132" width="12" height="12" /> <rect x="216" y="132" width="12" height="12" /> <rect x="228" y="132" width="12" height="12" /> <rect x="264" y="132" width="12" height="12" /> <rect x="276" y="132" width="12" height="12" /> <rect x="0" y="144" width="12" height="12" /> <rect x="36" y="144" width="12" height="12" /> <rect x="72" y="144" width="12" height="12" /> <rect x="84" y="144" width="12" height="12" /> <rect x="96" y="144" width="12" height="12" /> <rect x="120" y="144" width="12" height="12" /> <rect x="168" y="144" width="12" height="12" /> <rect x="192" y="144" width="12" height="12" /> <rect x="204" y="144" width="12" height="12" /> <rect x="216" y="144" width="12" height="12" /> <rect x="252" y="144" width="12" height="12" /> <rect x="264" y="144" width="12" height="12" /> <rect x="276" y="144" width="12" height="12" /> <rect x="288" y="144" width="12" height="12" /> <rect x="0" y="156" width="12" height="12" /> <rect x="12" y="156" width="12" height="12" /> <rect x="24" y="156" width="12" height="12" /> <rect x="84" y="156" width="12" height="12" /> <rect x="96" y="156" width="12" height="12" /> <rect x="132" y="156" width="12" height="12" /> <rect x="144" y="156" width="12" height="12" /> <rect x="168" y="156" width="12" height="12" /> <rect x="180" y="156" width="12" height="12" /> <rect x="192" y="156" width="12" height="12" /> <rect x="204" y="156" width="12" height="12" /> <rect x="240" y="156" width="12" height="12" /> <rect x="276" y="156" width="12" height="12" /> <rect x="24" y="168" width="12" height="12" /> <rect x="60" y="168" width="12" height="12" /> <rect x="72" y="168" width="12" height="12" /> <rect x="84" y="168" width="12" height="12" /> <rect x="108" y="168" width="12" height="12" /> <rect x="132" y="168" width="12" height="12" /> <rect x="156" y="168" width="12" height="12" /> <rect x="168" y="168" width="12" height="12" /> <rect x="180" y="168" width="12" height="12" /> <rect x="192" y="168" width="12" height="12" /> <rect x="228" y="168" width="12" height="12" /> <rect x="240" y="168" width="12" height="12" /> <rect x="252" y="168" width="12" height="12" /> <rect x="264" y="168" width="12" height="12" /> <rect x="24" y="180" width="12" height="12" /> <rect x="36" y="180" width="12" height="12" /> <rect x="60" y="180" width="12" height="12" /> <rect x="120" y="180" width="12" height="12" /> <rect x="168" y="180" width="12" height="12" /> <rect x="180" y="180" width="12" height="12" /> <rect x="216" y="180" width="12" height="12" /> <rect x="228" y="180" width="12" height="12" /> <rect x="240" y="180" width="12" height="12" /> <rect x="264" y="180" width="12" height="12" /> <rect x="276" y="180" width="12" height="12" /> <rect x="0" y="192" width="12" height="12" /> <rect x="12" y="192" width="12" height="12" /> <rect x="36" y="192" width="12" height="12" /> <rect x="48" y="192" width="12" height="12" /> <rect x="60" y="192" width="12" height="12" /> <rect x="72" y="192" width="12" height="12" /> <rect x="84" y="192" width="12" height="12" /> <rect x="96" y="192" width="12" height="12" /> <rect x="108" y="192" width="12" height="12" /> <rect x="168" y="192" width="12" height="12" /> <rect x="192" y="192" width="12" height="12" /> <rect x="204" y="192" width="12" height="12" /> <rect x="216" y="192" width="12" height="12" /> <rect x="228" y="192" width="12" height="12" /> <rect x="240" y="192" width="12" height="12" /> <rect x="252" y="192" width="12" height="12" /> <rect x="264" y="192" width="12" height="12" /> <rect x="96" y="204" width="12" height="12" /> <rect x="132" y="204" width="12" height="12" /> <rect x="144" y="204" width="12" height="12" /> <rect x="192" y="204" width="12" height="12" /> <rect x="240" y="204" width="12" height="12" /> <rect x="0" y="216" width="12" height="12" /> <rect x="12" y="216" width="12" height="12" /> <rect x="24" y="216" width="12" height="12" /> <rect x="36" y="216" width="12" height="12" /> <rect x="48" y="216" width="12" height="12" /> <rect x="60" y="216" width="12" height="12" /> <rect x="72" y="216" width="12" height="12" /> <rect x="108" y="216" width="12" height="12" /> <rect x="132" y="216" width="12" height="12" /> <rect x="192" y="216" width="12" height="12" /> <rect x="216" y="216" width="12" height="12" /> <rect x="240" y="216" width="12" height="12" /> <rect x="0" y="228" width="12" height="12" /> <rect x="72" y="228" width="12" height="12" /> <rect x="96" y="228" width="12" height="12" /> <rect x="132" y="228" width="12" height="12" /> <rect x="168" y="228" width="12" height="12" /> <rect x="192" y="228" width="12" height="12" /> <rect x="240" y="228" width="12" height="12" /> <rect x="252" y="228" width="12" height="12" /> <rect x="264" y="228" width="12" height="12" /> <rect x="288" y="228" width="12" height="12" /> <rect x="0" y="240" width="12" height="12" /> <rect x="24" y="240" width="12" height="12" /> <rect x="36" y="240" width="12" height="12" /> <rect x="48" y="240" width="12" height="12" /> <rect x="72" y="240" width="12" height="12" /> <rect x="96" y="240" width="12" height="12" /> <rect x="120" y="240" width="12" height="12" /> <rect x="132" y="240" width="12" height="12" /> <rect x="168" y="240" width="12" height="12" /> <rect x="192" y="240" width="12" height="12" /> <rect x="204" y="240" width="12" height="12" /> <rect x="216" y="240" width="12" height="12" /> <rect x="228" y="240" width="12" height="12" /> <rect x="240" y="240" width="12" height="12" /> <rect x="252" y="240" width="12" height="12" /> <rect x="264" y="240" width="12" height="12" /> <rect x="0" y="252" width="12" height="12" /> <rect x="24" y="252" width="12" height="12" /> <rect x="36" y="252" width="12" height="12" /> <rect x="48" y="252" width="12" height="12" /> <rect x="72" y="252" width="12" height="12" /> <rect x="132" y="252" width="12" height="12" /> <rect x="144" y="252" width="12" height="12" /> <rect x="156" y="252" width="12" height="12" /> <rect x="180" y="252" width="12" height="12" /> <rect x="216" y="252" width="12" height="12" /> <rect x="228" y="252" width="12" height="12" /> <rect x="264" y="252" width="12" height="12" /> <rect x="276" y="252" width="12" height="12" /> <rect x="288" y="252" width="12" height="12" /> <rect x="0" y="264" width="12" height="12" /> <rect x="24" y="264" width="12" height="12" /> <rect x="36" y="264" width="12" height="12" /> <rect x="48" y="264" width="12" height="12" /> <rect x="72" y="264" width="12" height="12" /> <rect x="120" y="264" width="12" height="12" /> <rect x="132" y="264" width="12" height="12" /> <rect x="156" y="264" width="12" height="12" /> <rect x="204" y="264" width="12" height="12" /> <rect x="216" y="264" width="12" height="12" /> <rect x="252" y="264" width="12" height="12" /> <rect x="276" y="264" width="12" height="12" /> <rect x="0" y="276" width="12" height="12" /> <rect x="72" y="276" width="12" height="12" /> <rect x="96" y="276" width="12" height="12" /> <rect x="108" y="276" width="12" height="12" /> <rect x="144" y="276" width="12" height="12" /> <rect x="168" y="276" width="12" height="12" /> <rect x="180" y="276" width="12" height="12" /> <rect x="216" y="276" width="12" height="12" /> <rect x="228" y="276" width="12" height="12" /> <rect x="240" y="276" width="12" height="12" /> <rect x="252" y="276" width="12" height="12" /> <rect x="264" y="276" width="12" height="12" /> <rect x="276" y="276" width="12" height="12" /> <rect x="0" y="288" width="12" height="12" /> <rect x="12" y="288" width="12" height="12" /> <rect x="24" y="288" width="12" height="12" /> <rect x="36" y="288" width="12" height="12" /> <rect x="48" y="288" width="12" height="12" /> <rect x="60" y="288" width="12" height="12" /> <rect x="72" y="288" width="12" height="12" /> <rect x="96" y="288" width="12" height="12" /> <rect x="120" y="288" width="12" height="12" /> <rect x="168" y="288" width="12" height="12" /> <rect x="180" y="288" width="12" height="12" /> <rect x="264" y="288" width="12" height="12" /> <rect x="276" y="288" width="12" height="12" /> <rect x="288" y="288" width="12" height="12" /> </g> </svg> </div> </div> </div> <a class="close-reveal-modal" aria-label="Close"> <i class="material-icons">clear</i> </a> </div> <a href="#" class="back-to-top"><span class="show-for-medium-up">Back to Top</span><span class="show-for-small">Top</span></a> <script data-cfasync="false" src="/cdn-cgi/scripts/5c5dd728/cloudflare-static/email-decode.min.js"></script><script src="https://pub.mdpi-res.com/assets/js/modernizr-2.8.3.min.js?5227e0738f7f421d?1739771134"></script> <script src="https://pub.mdpi-res.com/assets/js/jquery-1.12.4.min.js?4f252523d4af0b47?1739771134"></script> <script src="https://pub.mdpi-res.com/assets/js/foundation-5.5.3.min.js?6b2ec41c18b29054?1739771134"></script> <script src="https://pub.mdpi-res.com/assets/js/foundation-5.5.3.equalizer.min.js?0f6c549b75ec554c?1739771134"></script> <script src="https://pub.mdpi-res.com/assets/js/jquery.multiselect.js?0edd3998731d1091?1739771134"></script> <script src="https://pub.mdpi-res.com/assets/js/jquery.cycle2.min.js?63413052928f97ee?1739771134"></script> <script> // old browser fix - this way the console log rows won't throw (silent) errors in browsers not supporting console log if (!window.console) window.console = {}; if (!window.console.log) window.console.log = function () { }; var currentJournalNameSystem = "cancers"; $(document).ready(function() { $('select.foundation-select').multiselect({ search: true, minHeight: 130, maxHeight: 130, }); $(document).foundation({ orbit: { timer_speed: 4000, }, reveal: { animation: 'fadeAndPop', animation_speed: 100, } }); $(".chosen-select").each(function(element) { var maxSelected = (undefined !== $(this).data('maxselectedoptions') ? $(this).data('maxselectedoptions') : 100); $(this).on('chosen:ready', function(event, data) { var select = $(data.chosen.form_field); if (select.attr('id') === 'journal-browser-volume') { $(data.chosen.dropdown).addClass('UI_JournalBrowser_Volume_Options'); } if (select.attr('id') === 'journal-browser-issue') { $(data.chosen.dropdown).addClass('UI_JournalBrowser_Issue_Options'); } }).chosen({ display_disabled_options: false, disable_search_threshold: 7, max_selected_options: maxSelected, width: "100%" }); }); $(".toEncode").each(function(e) { var oldHref = $(this).attr("href"); var newHref = oldHref.replace('.botdefense.please.enable.javascript.','@'); $(this).attr("href", newHref); if (!$(this).hasClass("emailCaptcha")) { $(this).html(newHref.replace('mailto:', '')); } $(this).removeClass("visibility-hidden"); }); $(document).on('opened.fndtn.reveal', '[data-reveal]', function() { $(document).foundation('equalizer', 'reflow'); }); // fix the images that have tag height / width defined // otherwise the default foundation styles overwrite the tag definitions $("img").each(function() { if ($(this).attr('width') != undefined || $(this).attr('height') != undefined) { $(this).addClass("img-fixed"); } }); $("#basic_search, #advanced_search").submit(function(e) { var searchArguments = false; $(this).find("input,select").not("#search,.search-button").each(function() { if (undefined === $(this).val() || "" === $(this).val()) { $(this).attr('name', null); } else { $(this).attr('name'); searchArguments = true; } }); if (!searchArguments) { window.location = $(this).attr('action'); return false; } }); $(".hide-show-desktop-option").click(function(e) { e.preventDefault(); var parentDiv = $(this).closest("div"); $.ajax({ url: $(this).attr('href'), success: function(msg) { parentDiv.removeClass().hide(); } }); }); $(".generic-toggleable-header").click(function(e) { $(this).toggleClass("active"); $(this).next(".generic-toggleable-content").toggleClass("active"); }); /* * handle whole row as a link if the row contains only one visible link */ $("table.new tr").hover(function() { if ($(this).find("td:visible a").length == 1) { $(this).addClass("single-link"); } }, function() { $(this).removeClass("single-link"); }); $("table.new:not(.table-of-tables)").on("click", "tr.single-link", function(e) { var target = $(e.target); if (!e.ctrlKey && !target.is("a")) { $(this).find("td:visible a")[0].click(); } }); $(document).on("click", ".custom-accordion-for-small-screen-link", function(e) { if ($(this).closest("#basic_search").length > 0) { if ($(".search-container__advanced").first().is(":visible")) { openAdvanced() } } if (Foundation.utils.is_small_only()) { if ($(this).hasClass("active")) { $(this).removeClass("active"); $(this).next(".custom-accordion-for-small-screen-content").addClass("show-for-medium-up"); } else { $(this).addClass("active"); $(this).next(".custom-accordion-for-small-screen-content").removeClass("show-for-medium-up"); $(document).foundation('orbit', 'reflow'); } } if (undefined !== $(this).data("callback")) { var customCallback = $(this).data("callback"); func = window[customCallback]; func(); } }); $(document).on("click", ".js-open-small-search", function(e) { e.preventDefault(); $(this).toggleClass("active").closest(".tab-bar").toggleClass("active"); $(".search-container").toggleClass("hide-for-small-down"); }); $(document).on("click", ".js-open-menu", function(e) { $(".search-container").addClass("hide-for-small-down"); }); $(window).on('resize', function() { recalculate_main_browser_position(); recalculate_responsive_moving_containers(); }); updateSearchLabelVisibilities(); recalculate_main_browser_position(); recalculate_responsive_moving_containers(); if (window.document.documentMode == 11) { $("<link/>", { rel: "stylesheet", type: "text/css", href: "https://fonts.googleapis.com/icon?family=Material+Icons"}).appendTo("head"); } }); function recalculate_main_browser_position() { if (Foundation.utils.is_small_only()) { if ($("#js-main-top-container").parent("#js-large-main-top-container").length > 0) { $("#js-main-top-container").appendTo($("#js-small-main-top-container")); } } else { if ($("#js-main-top-container").parent("#js-small-main-top-container").length > 0) { $("#js-main-top-container").appendTo($("#js-large-main-top-container")); } } } function recalculate_responsive_moving_containers() { $(".responsive-moving-container.large").each(function() { var previousParent = $(".responsive-moving-container.active[data-id='"+$(this).data("id")+"']"); var movingContent = previousParent.html(); if (Foundation.utils.is_small_only()) { var currentParent = $(".responsive-moving-container.small[data-id='"+$(this).data("id")+"']"); } else if (Foundation.utils.is_medium_only()) { var currentParent = $(".responsive-moving-container.medium[data-id='"+$(this).data("id")+"']"); } else { var currentParent = $(".responsive-moving-container.large[data-id='"+$(this).data("id")+"']"); } if (previousParent.attr("class") !== currentParent.attr("class")) { currentParent.html(movingContent); previousParent.html(); currentParent.addClass("active"); previousParent.removeClass("active"); } }); } // cookies allowed is checked from a) local storage and b) from server separately so that the footer bar doesn't // get included in the custom page caches function checkCookiesAllowed() { var cookiesEnabled = localStorage.getItem("mdpi_cookies_enabled"); if (null === cookiesEnabled) { $.ajax({ url: "/ajax_cookie_value/mdpi_cookies_accepted", success: function(data) { if (data.value) { localStorage.setItem("mdpi_cookies_enabled", true); checkDisplaySurvey(); } else { $(".js-allow-cookies").show(); } } }); } else { checkDisplaySurvey(); } } function checkDisplaySurvey() { } window.addEventListener('CookiebotOnAccept', function (e) { var CookieDate = new Date; if (Cookiebot.consent.preferences) { CookieDate.setFullYear(CookieDate.getFullYear() + 1); document.cookie = "mdpi_layout_type_v2=mobile; path=/; expires=" + CookieDate.toUTCString() + ";"; $(".js-toggle-desktop-layout-link").css("display", "inline-block"); } }, false); window.addEventListener('CookiebotOnDecline', function (e) { if (!Cookiebot.consent.preferences) { $(".js-toggle-desktop-layout-link").hide(); if ("" === "desktop") { window.location = "/toggle_desktop_layout_cookie"; } } }, false); var hash = $(location).attr('hash'); if ("#share" === hash) { if (1 === $("#main-share-modal").length) { $('#main-share-modal').foundation('reveal', 'open'); } } </script> <script src="https://pub.mdpi-res.com/assets/js/lib.js?b86ef680a60436c6?1739771134"></script> <script src="https://pub.mdpi-res.com/assets/js/mdpi.js?c267ce58392b15da?1739771134"></script> <script>var banners_url = 'https://serve.mdpi.com';</script> <script type='text/javascript' src='https://pub.mdpi-res.com/assets/js/ifvisible.min.js?c621d19ecb761212?1739771134'></script> <script src="https://pub.mdpi-res.com/assets/js/xmltohtml/affix.js?ac4ea55275297c15?1739771134"></script> <script src="https://pub.mdpi-res.com/assets/js/clipboard.min.js?3f3688138a1b9fc4?1739771134"></script> <script type="text/javascript"> $(document).ready(function() { var helpFunctions = $(".middle-column__help__fixed"); var leftColumnAffix = $(".left-column__fixed"); var middleColumn = $("#middle-column"); var clone = null; helpFunctions.affix({ offset: { top: function() { return middleColumn.offset().top - 8 - (Foundation.utils.is_medium_only() ? 30 : 0); }, bottom: function() { return $("#footer").innerHeight() + 74 + (Foundation.utils.is_medium_only() ? 0 : 0); } } }); if (leftColumnAffix.length > 0) { clone = leftColumnAffix.clone(); clone.addClass("left-column__fixed__affix"); clone.insertBefore(leftColumnAffix); clone.css('width', leftColumnAffix.outerWidth() + 50); clone.affix({ offset: { top: function() { return leftColumnAffix.offset().top - 30 - (Foundation.utils.is_medium_only() ? 50 : 0); }, bottom: function() { return $("#footer").innerHeight() + 92 + (Foundation.utils.is_medium_only() ? 0 : 0); } } }); } $(window).on("resize", function() { if (clone !== null) { clone.css('width', leftColumnAffix.outerWidth() + 50); } }); new ClipboardJS('.js-clipboard-copy'); }); </script> <script src="https://pub.mdpi-res.com/assets/js/jquery-ui-1.13.2.min.js?1e2047978946a1d2?1739771134"></script> <script src="https://pub.mdpi-res.com/assets/js/slick.min.js?d5a61c749e44e471?1739771134"></script> <script> $(document).ready(function() { $(".link-article-menu").click(function(e) { e.preventDefault(); $(this).find('span').toggle(); $(this).next("div").toggleClass("active"); }); $(".js-similarity-related-articles").click(function(e) { e.preventDefault(); if ('' !== $('#recommended-articles-modal').attr('data-url')) { $('#recommended-articles-modal').foundation('reveal', 'open', $('#recommended-articles-modal').attr('data-url')); } }); $.ajax({ url: "/article/468413/similarity-related/show-link", success: function(result) { if (result.show) { $('#recommended-articles-modal').attr('data-url', result.link); $('.js-article-similarity-container').show(); } } }); $("#recommended-articles-modal").on("click", ".ga-title-link-recommended-article", function(e) { var clickEventUrl = $(this).data("click-event-url"); if (typeof clickEventUrl !== "undefined") { fetch(clickEventUrl, { method: "GET", mode: "no-cors" }); } }); $(document).on('opened.fndtn.reveal', '[data-reveal]', function() { var modal = $(this); if (modal.attr('id') === "author-biographies-modal") { modal.find('.multiple-items').slick({ slidesToShow: 1, nextArrow: '<a class="slick-next" href="#"><i class="material-icons">chevron_right</i></a>', prevArrow: '<a class="slick-prev" href="#"><i class="material-icons">chevron_left</i></a>', slidesToScroll: 1, draggable: false, }); modal.find('.multiple-items').slick('refresh'); } }); }); </script> <script type="text/javascript"> if (-1 !== window.location.href.indexOf("?src=")) { window.history.replaceState({}, '', `${location.pathname}`); } $(document).ready(function() { var scifeedCounter = 0; var search = window.location.search; var mathjaxReady = false; // late image file loading $("img[data-lsrc]").each(function() { $(this).attr("src", $(this).data("lsrc")); }); // late mathjax initialization var head = document.getElementsByTagName("head")[0]; var script = document.createElement("script"); script.type = "text/x-mathjax-config"; script[(window.opera ? "innerHTML" : "text")] = "MathJax.Hub.processSectionDelay = 0;\n" + "MathJax.Hub.Config({\n" + " \"menuSettings\": {\n" + " CHTMLpreview: false\n" + " },\n" + " \"CHTML-preview\":{\n" + " disabled: true\n" + " },\n" + " \"HTML-CSS\": {\n" + " scale: 90,\n" + " availableFonts: [],\n" + " preferredFont: null,\n" + " preferredFonts: null,\n" + " webFont:\"Gyre-Pagella\",\n" + " imageFont:'TeX',\n" + " undefinedFamily:\"'Arial Unicode MS',serif\",\n" + " linebreaks: { automatic: false }\n" + " },\n" + " \"TeX\": {\n" + " extensions: ['noErrors.js'],\n" + " noErrors: {\n" + " inlineDelimiters: [\"\",\"\"],\n" + " multiLine: true,\n" + " style: {\n" + " 'font-size': '90%',\n" + " 'text-align': 'left',\n" + " 'color': 'black',\n" + " 'padding': '1px 3px',\n" + " 'border': '1px solid'\n" + " }\n" + " }\n" + " }\n" + "});\n" + "MathJax.Hub.Register.StartupHook('End', function() {\n" + " refreshMathjaxWidths();\n" + " mathjaxReady = true;\n" + "});\n" + "MathJax.Hub.Startup.signal.Interest(function (message) {\n" + " if (message == 'End') {\n" + " var hypoLink = document.getElementById('hypothesis_frame');\n" + " if (null !== hypoLink) {\n" + " hypoLink.setAttribute('src', 'https://commenting.mdpi.com/embed.js');\n" + " }\n" + " }\n" + "});"; head.appendChild(script); script = document.createElement("script"); script.type = "text/javascript"; script.src = "https://pub.mdpi-res.com/bundles/mathjax/MathJax.js?config=TeX-AMS-MML_HTMLorMML"; head.appendChild(script); // article version checker if (0 === search.indexOf('?type=check_update&version=')) { $.ajax({ url: "/2072-6694/13/1/43" + "/versioncheck" + search, success: function(result) { $(".js-check-update-container").html(result); } }); } $('#feed_option').click(function() { // tracker if ($('#scifeed_clicked').length<1) { $(this).append('<span style="display:none" id="scifeed_clicked">done</span>'); } $('#feed_data').toggle('slide', { direction: 'up'}, '1000'); // slideToggle(700); OR toggle(700) $("#scifeed_error_msg").html('').hide(); $("#scifeed_notice_msg").html('').hide(); }); $('#feed_option').click(function(event) { setTimeout(function(){ var captchaSection = $("#captchaSection"); captchaSection.removeClass('ui-helper-hidden').find('input').prop('disabled', false); // var img = captchaSection.find('img'); // img.attr('src', img.data('url') + "?" + (new Date()).getTime()); // $(".captcha_reload").trigger("click"); var img = document.getElementById('gregwar_captcha_scifeed'); img.src = '/generate-captcha/gcb_captcha?n=' + (new Date()).getTime(); },800); }); $(document).on('click', '.split_feeds', function() { var name = $( this ).attr('name'); var flag = 1 - ($(this).is(":checked")*1); $('.split_feeds').each(function (index) { if ($( this ).attr('name') !== name) { $(this)[0].checked = flag; } }); }); $(document).on('click', '#scifeed_submit, #scifeed_submit1', function(event) { event.preventDefault(); $(".captcha_reload").trigger("click"); $("#scifeed_error_msg").html(""); $("#scifeed_error_msg").hide(); }); $(document).on('click', '.subscription_toggle', function(event) { if ($(this).val() === 'Create SciFeed' && $('#scifeed_hidden_flag').length>0) { event.preventDefault(); // alert('Here there would be a captcha because user is not logged in'); var captchaSection = $("#captchaSection"); if (captchaSection.hasClass('ui-helper-hidden')) { captchaSection.removeClass('ui-helper-hidden').find('input').prop('disabled', false); var img = captchaSection.find('img'); img.attr('src', img.data('url') + "?" + (new Date()).getTime()); $("#reloadCaptcha").trigger("click"); } } }); $(document).on('click', '.scifeed_msg', function(){ $(this).hide(); }); $(document).on('click', '.article-scilit-search', function(e) { e.preventDefault(); var data = $(".article-scilit-search-data").val(); var dataArray = data.split(';').map(function(keyword) { return "(\"" + keyword.trim() + "\")"; }); var searchQuery = dataArray.join(" OR "); var searchUrl = encodeURI("https://www.scilit.com/articles/search?q="+ searchQuery + "&advanced=1&highlight=1"); var win = window.open(searchUrl, '_blank'); if (win) { win.focus(); } else { window.location(searchUrl); } }); display_stats(); citedCount(); follow_goto(); // Select the node that will be observed for mutations const targetNodes = document.getElementsByClassName('hypothesis-count-container'); // Options for the observer (which mutations to observe) const config = { attributes: false, childList: true, subtree: false }; // Callback function to execute when mutations are observed const callback = function(mutationList, observer) { for(const mutation of mutationList) { if (mutation.type === 'childList') { let node = $(mutation.target); if (parseInt(node.html()) > 0) { node.show(); } } } }; // Create an observer instance linked to the callback function const observer = new MutationObserver(callback); // Start observing the target node for configured mutations for(const targetNode of targetNodes) { observer.observe(targetNode, config); } // Select the node that will be observed for mutations const mathjaxTargetNode = document.getElementById('middle-column'); // Callback function to execute when mutations are observed const mathjaxCallback = function(mutationList, observer) { if (mathjaxReady && typeof(MathJax) !== 'undefined') { refreshMathjaxWidths(); } }; // Create an observer instance linked to the callback function const mathjaxObserver = new ResizeObserver(mathjaxCallback); // Start observing the target node for configured mutations mathjaxObserver.observe(mathjaxTargetNode); }); /* END $(document).ready */ function refreshMathjaxWidths() { let width = ($('.html-body').width()*0.9) + "px"; $('.MathJax_Display').css('max-width', width); $('.MJXc-display').css('max-width', width); } function sendScifeedFrom(form) { if (!$('#scifeed_email').val().trim()) { // empty email alert('Please, provide an email for subscribe to this scifeed'); return false; } else if (!$('#captchaSection').hasClass('ui-helper-hidden') && !$('#captchaSection').find('input').val().trim()) { // empty captcha alert('Please, fill the captcha field.'); return false; } else if( ((($('#scifeed_form').find('input:checkbox:checked').length)-($('#split_feeds:checked').length))<1) || ($('#scifeed_kwd_txt').length < 0 && !$('#scifeed_kwd_txt').val().trim()) || ($('#scifeed_author_txt').length<0 &&!$('#scifeed_author_txt').val().trim()) ) { alert('You did not select anything to subscribe'); return false; } else if(($('#scifeed_form').find('input:checkbox:checked').length)-($('#split_feeds2:checked').length)<1){ alert("You did not select anything to subscribe"); return false; } else { var url = $('#scifeed_subscribe_url').html(); var formData = $(form).serializeArray(); $.post(url, formData).done(function (data) { if (JSON.parse(data)) { $('.scifeed_msg').hide(); var res = JSON.parse(data); var successFeeds = 0; var errorFeeds = 0; if (res) { $('.scifeed_msg').html(''); $.each(res, function (index, val) { if (val) { if (val.error) { errorFeeds++; $("#scifeed_error_msg").append(index+' - '+val.error+'<br>'); } if (val.notice) // for successful feed creation { successFeeds++; // $("#scifeed_notice_msg").append(index+' - '+val.notice+'<br>'); $("#scifeed_notice_msg").append('<li>'+index+'</li>'); } } }); if (successFeeds>0) { text = $('#scifeed_notice_msg').html(); text = 'The following feed'+(successFeeds>1?'s have':' has')+ ' been sucessfully created:<br><ul>'+ text + '</ul>' +($('#scifeed_hidden_flag').length>0 ? 'You are not logged in, so you probably need to validate '+ (successFeeds>1?'them':' it')+'.<br>' :'' ) +'Please check your email'+(successFeeds>1?'s':'')+' for more details.'; //(successFeeds>1?' for each of them':'')+'.<br>'; $("#scifeed_notice_msg").html(text); $("#scifeed_notice_msg").show(); } if (errorFeeds>0) { $("#scifeed_error_msg").show();; } } $("#feed_data").hide(); } }); } } function follow_goto() { var hashStr = location.hash.replace("#",""); if(typeof hashStr !== 'undefined') { if( hashStr == 'supplementary') { document.getElementById('suppl_id').scrollIntoView(); } if( hashStr == 'citedby') { document.getElementById('cited_id').scrollIntoView(); } } } function cited() { $("#framed_div").toggle('fast', function(){ if ($(this).css('display') != 'none') { var loaded = document.getElementById("loaded"); if(loaded.innerHTML == "No") { // Load Xref result var container = document.getElementById("framed_div"); // This replace the content container.innerHTML = "<img src=\"https://pub.mdpi-res.com/img/loading_circle.gif?9a82694213036313?1739771134\" height=\"20\" width=\"20\" alt=\"Processing...\" style=\"vertical-align:middle; margin-right:0.6em;\">"; var url = "/citedby/10.3390%252Fcancers13010043/23"; $.post(url, function(result) { if (result.success) { container.innerHTML = result.view; } loaded.innerHTML = "Yes"; }); } } return true; // for not going at the beginning of the page... }) return true; // for not going at the beginning of the page... } function detect_device() { // Added by Bastien (18/08/2014): based on the http://detectmobilebrowsers.com/ detector var check = false; (function(a){if(/(android|bb\d+|meego).+mobile|avantgo|bada\/|blackberry|blazer|compal|elaine|fennec|hiptop|iemobile|ip(hone|od)|iris|kindle|lge |maemo|midp|mmp|mobile.+firefox|netfront|opera m(ob|in)i|palm( os)?|phone|p(ixi|re)\/|plucker|pocket|psp|series(4|6)0|symbian|treo|up\.(browser|link)|vodafone|wap|windows (ce|phone)|xda|xiino/i.test(a)||/1207|6310|6590|3gso|4thp|50[1-6]i|770s|802s|a wa|abac|ac(er|oo|s\-)|ai(ko|rn)|al(av|ca|co)|amoi|an(ex|ny|yw)|aptu|ar(ch|go)|as(te|us)|attw|au(di|\-m|r |s )|avan|be(ck|ll|nq)|bi(lb|rd)|bl(ac|az)|br(e|v)w|bumb|bw\-(n|u)|c55\/|capi|ccwa|cdm\-|cell|chtm|cldc|cmd\-|co(mp|nd)|craw|da(it|ll|ng)|dbte|dc\-s|devi|dica|dmob|do(c|p)o|ds(12|\-d)|el(49|ai)|em(l2|ul)|er(ic|k0)|esl8|ez([4-7]0|os|wa|ze)|fetc|fly(\-|_)|g1 u|g560|gene|gf\-5|g\-mo|go(\.w|od)|gr(ad|un)|haie|hcit|hd\-(m|p|t)|hei\-|hi(pt|ta)|hp( i|ip)|hs\-c|ht(c(\-| |_|a|g|p|s|t)|tp)|hu(aw|tc)|i\-(20|go|ma)|i230|iac( |\-|\/)|ibro|idea|ig01|ikom|im1k|inno|ipaq|iris|ja(t|v)a|jbro|jemu|jigs|kddi|keji|kgt( |\/)|klon|kpt |kwc\-|kyo(c|k)|le(no|xi)|lg( g|\/(k|l|u)|50|54|\-[a-w])|libw|lynx|m1\-w|m3ga|m50\/|ma(te|ui|xo)|mc(01|21|ca)|m\-cr|me(rc|ri)|mi(o8|oa|ts)|mmef|mo(01|02|bi|de|do|t(\-| |o|v)|zz)|mt(50|p1|v )|mwbp|mywa|n10[0-2]|n20[2-3]|n30(0|2)|n50(0|2|5)|n7(0(0|1)|10)|ne((c|m)\-|on|tf|wf|wg|wt)|nok(6|i)|nzph|o2im|op(ti|wv)|oran|owg1|p800|pan(a|d|t)|pdxg|pg(13|\-([1-8]|c))|phil|pire|pl(ay|uc)|pn\-2|po(ck|rt|se)|prox|psio|pt\-g|qa\-a|qc(07|12|21|32|60|\-[2-7]|i\-)|qtek|r380|r600|raks|rim9|ro(ve|zo)|s55\/|sa(ge|ma|mm|ms|ny|va)|sc(01|h\-|oo|p\-)|sdk\/|se(c(\-|0|1)|47|mc|nd|ri)|sgh\-|shar|sie(\-|m)|sk\-0|sl(45|id)|sm(al|ar|b3|it|t5)|so(ft|ny)|sp(01|h\-|v\-|v )|sy(01|mb)|t2(18|50)|t6(00|10|18)|ta(gt|lk)|tcl\-|tdg\-|tel(i|m)|tim\-|t\-mo|to(pl|sh)|ts(70|m\-|m3|m5)|tx\-9|up(\.b|g1|si)|utst|v400|v750|veri|vi(rg|te)|vk(40|5[0-3]|\-v)|vm40|voda|vulc|vx(52|53|60|61|70|80|81|83|85|98)|w3c(\-| )|webc|whit|wi(g |nc|nw)|wmlb|wonu|x700|yas\-|your|zeto|zte\-/i.test(a.substr(0,4)))check = true})(navigator.userAgent||navigator.vendor||window.opera); return check; } function display_stats(){ $("#article_stats_div").toggle(); return false; } /* * Cited By Scopus */ function citedCount(){ $("#framed_div_cited_count").toggle('fast', function(){ if ($(this).css('display') != 'none') { var loaded = document.getElementById("loaded_cite_count"); // to load only once the result! if(loaded.innerHTML == "No") { // Load Xref result var d = document.getElementById("framed_div_cited_count"); // This replace the content d.innerHTML = "<img src=\"https://pub.mdpi-res.com/img/loading_circle.gif?9a82694213036313?1739771134\" height=\"20\" width=\"20\" alt=\"Processing...\" style=\"vertical-align:middle; margin-right:0.6em;\">"; $.ajax({ method : "POST", url : "/cite-count/10.3390%252Fcancers13010043", success : function(data) { if (data.succ) { d.innerHTML = data.view; loaded.innerHTML = "Yes"; follow_goto(); } } }); } } // end else return true; // for not going at the beginning of the page... }) return true; // for not going at the beginning of the page... } </script><script type="text/javascript" src="https://pub.mdpi-res.com/assets/js/third-party/highcharts/highcharts.js?bdd06f45e34c33df?1739771134"></script><script type="text/javascript" src="https://pub.mdpi-res.com/assets/js/third-party/highcharts/modules/exporting.js?944dc938d06de3a8?1739771134"></script><script type="text/javascript" defer="defer"> var advancedStatsData; var selectedStatsType = "abstract"; $(function(){ var countWrapper = $('#counts-wrapper'); $('#author_stats_id #type_links a').on('click', function(e) { e.preventDefault(); selectedStatsType = $(this).data('type'); $('#article_advanced_stats').vectorMap('set', 'values', advancedStatsData[selectedStatsType]); $('#advanced_stats_max').html(advancedStatsData[selectedStatsType].max); $('#type_links a').removeClass('active'); $(this).addClass('active'); }); $.get('/2072-6694/13/1/43/stats', function (result) { if (!result.success) { return; } // process article metrics part in left column var viewNumber = countWrapper.find(".view-number"); viewNumber.html(result.metrics.views); viewNumber.parent().toggleClass("count-div--grey", result.metrics.views == 0); var downloadNumber = countWrapper.find(".download-number"); downloadNumber.html(result.metrics.downloads); downloadNumber.parent().toggleClass("count-div--grey", result.metrics.downloads == 0); var citationsNumber = countWrapper.find(".citations-number"); citationsNumber.html(result.metrics.citations); citationsNumber.parent().toggleClass("count-div--grey", result.metrics.citations == 0); if (result.metrics.views > 0 || result.metrics.downloads > 0 || result.metrics.citations > 0) { countWrapper.find("#js-counts-wrapper__views, #js-counts-wrapper__downloads").addClass("visible").show(); if (result.metrics.citations > 0) { countWrapper.find('.citations-number').html(result.metrics.citations).show(); countWrapper.find("#js-counts-wrapper__citations").addClass("visible").show(); } else { countWrapper.find("#js-counts-wrapper__citations").remove(); } $("[data-id='article-counters']").removeClass("hidden"); } if (result.metrics.altmetrics_score > 0) { $("#js-altmetrics-donut").show(); } // process view chart in main column var jsondata = result.chart; var series = new Array(); $.each(jsondata.elements, function(i, element) { var dataValues = new Array(); $.each(element.values, function(i, value) { dataValues.push(new Array(value.tip, value.value)); }); series[i] = {name: element.text, data:dataValues}; }); Highcharts.setOptions({ chart: { style: { fontFamily: 'Arial,sans-serif' } } }); $('#article_stats_swf').highcharts({ chart: { type: 'line', width: $("#tabs").width() //* 0.91 }, credits: { enabled: false }, exporting: { enabled: true }, title: { text: jsondata.title.text, x: -20 //center }, xAxis: { categories: jsondata.x_axis.labels.labels, offset: jsondata.x_axis.offset, labels:{ step: jsondata.x_axis.labels.steps, rotation: 30 } }, yAxis: { max: jsondata.y_axis.max, min: jsondata.y_axis.min, offset: jsondata.y_axis.offset, labels: { steps: jsondata.y_axis.steps }, title: { enabled: false } }, tooltip: { formatter: function (){ return this.key.replace("#val#", this.y); } }, legend: { align: 'top', itemDistance: 50 }, series: series }); }); $('#supplement_link').click(function() { document.getElementById('suppl_id').scrollIntoView(); }); $('#stats_link').click(function() { document.getElementById('stats_id').scrollIntoView(); }); // open mol viewer for molbank special supplementary files $('.showJmol').click(function(e) { e.preventDefault(); var jmolModal = $("#jmolModal"); var url = "/article/468413/jsmol_viewer/__supplementary_id__"; url = url.replace(/__supplementary_id__/g, $(this).data('index')); $('#jsmol-content').attr('src', url); jmolModal.find(".content").html($(this).data('description')); jmolModal.foundation("reveal", "open"); }); }); !function() { "use strict"; function e(e) { try { if ("undefined" == typeof console) return; "error"in console ? console.error(e) : console.log(e) } catch (e) {} } function t(e) { return d.innerHTML = '<a href="' + e.replace(/"/g, """) + '"></a>', d.childNodes[0].getAttribute("href") || "" } function n(n, c) { var o = ""; var k = parseInt(n.substr(c + 4, 2), 16); for (var i = c; i < n.length; i += 2) { if (i != c + 4) { var s = parseInt(n.substr(i, 2), 16) ^ k; o += String.fromCharCode(s); } } try { o = decodeURIComponent(escape(o)); } catch (error) { console.error(error); } return t(o); } function c(t) { for (var r = t.querySelectorAll("a"), c = 0; c < r.length; c++) try { var o = r[c] , a = o.href.indexOf(l); a > -1 && (o.href = "mailto:" + n(o.href, a + l.length)) } catch (i) { e(i) } } function o(t) { for (var r = t.querySelectorAll(u), c = 0; c < r.length; c++) try { var o = r[c] , a = o.parentNode , i = o.getAttribute(f); if (i) { var l = n(i, 0) , d = document.createTextNode(l); a.replaceChild(d, o) } } catch (h) { e(h) } } function a(t) { for (var r = t.querySelectorAll("template"), n = 0; n < r.length; n++) try { i(r[n].content) } catch (c) { e(c) } } function i(t) { try { c(t), o(t), a(t) } catch (r) { e(r) } } var l = "/cnd-cgi/l/email-protection#" , u = ".__cf_email__" , f = "data-cfemail" , d = document.createElement("div"); i(document), function() { var e = document.currentScript || document.scripts[document.scripts.length - 1]; e.parentNode.removeChild(e) }() }(); </script><script type="text/javascript"> function setCookie(cname, cvalue, ctime) { ctime = (typeof ctime === 'undefined') ? 10*365*24*60*60*1000 : ctime; // default => 10 years var d = new Date(); d.setTime(d.getTime() + ctime); // ==> 1 hour = 60*60*1000 var expires = "expires="+d.toUTCString(); document.cookie = cname + "=" + cvalue + "; " + expires +"; path=/"; } function getCookie(cname) { var name = cname + "="; var ca = document.cookie.split(';'); for(var i=0; i<ca.length; i++) { var c = ca[i]; while (c.charAt(0)==' ') c = c.substring(1); if (c.indexOf(name) == 0) return c.substring(name.length, c.length); } return ""; } </script><script type="text/javascript" src="https://d1bxh8uas1mnw7.cloudfront.net/assets/embed.js"></script><script> $(document).ready(function() { if ($("#js-similarity-related-data").length > 0) { $.ajax({ url: '/article/468413/similarity-related', success: function(response) { $("#js-similarity-related-data").html(response); $("#js-related-articles-menu").show(); $(document).foundation('tab', 'reflow'); MathJax.Hub.Queue(["Typeset", MathJax.Hub]); } }); } }); </script><link rel="stylesheet" href="https://pub.mdpi-res.com/assets/css/jquery-ui-1.10.4.custom.min.css?80647d88647bf347?1739771134"><link rel="stylesheet" href="https://pub.mdpi-res.com/assets/css/magnific-popup.min.css?04d343e036f8eecd?1739771134"><script type="text/javascript" src="https://pub.mdpi-res.com/assets/js/magnific-popup.min.js?2be3d9e7dc569146?1739771134"></script><script> $(function() { $(".js-show-more-academic-editors").on("click", function(e) { e.preventDefault(); $(this).hide(); $(".academic-editor-container").removeClass("hidden"); }); }); </script> <link rel="stylesheet" href="https://pub.mdpi-res.com/assets/css/vmap/jqvmap.min.css?126a06688aa11c13?1739771134"> <script src="https://pub.mdpi-res.com/assets/js/vmap/jquery.vmap.min.js?935f68d33bdd88a1?1739771134"></script> <script src="https://pub.mdpi-res.com/assets/js/vmap/jquery.vmap.world.js?16677403c0e1bef1?1739771134"></script> <script> function updateSlick() { $('.multiple-items').slick('setPosition'); } $(document).ready(function() { $('.multiple-items').slick({ slidesToShow: 1, nextArrow: '<a class="slick-next" href="#"><i class="material-icons">chevron_right</i></a>', prevArrow: '<a class="slick-prev" href="#"><i class="material-icons">chevron_left</i></a>', slidesToScroll: 1, responsive: [ { breakpoint: 1024, settings: { slidesToShow: 1, slidesToScroll: 1, } }, { breakpoint: 600, settings: { slidesToShow: 1, slidesToScroll: 1, } }, { breakpoint: 480, settings: { slidesToShow: 1, slidesToScroll: 1, } } ] }); $('.multiple-items').show(); $(document).on('click', '.reviewReportSelector', function(e) { let path = $(this).attr('data-path'); handleReviews(path, $(this)); }); $(document).on('click', '.viewReviewReports', function(e) { let versionOne = $('#versionTab_1'); if (!versionOne.hasClass('activeTab')) { let path = $(this).attr('data-path'); handleReviews(path, versionOne); } location.href = "#reviewReports"; }); $(document).on('click', '.reviewersResponse, .authorResponse', function(e) { let version = $(this).attr('data-version'); let targetVersion = $('#versionTab_' + version); if (!targetVersion.hasClass('activeTab')) { let path = targetVersion.attr('data-path'); handleReviews(path, targetVersion); } location.href = $(this).attr('data-link'); }); $(document).on('click', '.tab', function (e) { e.preventDefault(); $('.tab').removeClass('activeTab'); $(this).addClass('activeTab') $('.tab').each(function() { $(this).closest('.tab-title').removeClass('active'); }); $(this).closest('.tab-title').addClass('active') }); }); function handleReviews(path, target) { $.ajax({ url: path, context: this, success: function (data) { $('.activeTab').removeClass('activeTab'); target.addClass('activeTab'); $('#reviewSection').html(data.view); }, error: function (xhr, ajaxOptions, thrownError) { console.log(xhr.status); console.log(thrownError); } }); } </script> <script src="https://pub.mdpi-res.com/assets/js/xmltohtml/affix.js?v1?1739771134"></script> <script src="https://pub.mdpi-res.com/assets/js/xmltohtml/storage.js?e9b262d3a3476d25?1739771134"></script> <script src="https://pub.mdpi-res.com/assets/js/xmltohtml/jquery-scrollspy.js?09cbaec0dbb35a67?1739771134"></script> <script src="https://pub.mdpi-res.com/assets/js/xmltohtml/magnific-popup.js?4a09c18460afb26c?1739771134"></script> <script src="https://pub.mdpi-res.com/assets/js/xmltohtml/underscore.js?f893e294cde60c24?1739771134"></script> <script type="text/javascript"> $('document').ready(function(){ $("#left-column").addClass("show-for-large-up"); $("#middle-column").removeClass("medium-9").removeClass("left-bordered").addClass("medium-12"); $(window).on('resize scroll', function() { /* if ($('.button--drop-down').isInViewport($(".top-bar").outerHeight())) { */ if ($('.button--drop-down').isInViewport()) { $("#js-button-download").hide(); } else { $("#js-button-download").show(); } }); }); $(document).on('DOMNodeInserted', function(e) { var element = $(e.target); if (element.hasClass('menu') && element.hasClass('html-nav') ) { element.addClass("side-menu-ul"); } }); </script> <script src="https://pub.mdpi-res.com/assets/js/xmltohtml/articles.js?5118449d9ad8913a?1739771134"></script> <script> repositionOpenSideBar = function() { $('#left-column').addClass("show-for-large-up show-for-medium-up").show(); $('#middle-column').removeClass('large-12').removeClass('medium-12'); $('#middle-column').addClass('large-9'); } repositionCloseSideBar = function() { $('#left-column').removeClass("show-for-large-up show-for-medium-up").hide(); $('#middle-column').removeClass('large-9'); $('#middle-column').addClass('large-12').addClass('medium-12'); } </script>   <script type="text/plain" data-cookieconsent="marketing"> !function(e,t,n,s,u,a){e.twq||(s=e.twq=function(){s.exe?s.exe.apply(s,arguments):s.queue.push(arguments); },s.version='1.1',s.queue=[],u=t.createElement(n),u.async=!0,u.src='//static.ads-twitter.com/uwt.js', a=t.getElementsByTagName(n)[0],a.parentNode.insertBefore(u,a))}(window,document,'script'); // Insert Twitter Pixel ID and Standard Event data below twq('init','o2pip'); twq('track','PageView'); </script>  <script>(function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'9134ec738b8af8ec',t:'MTczOTc4NjM1Ni4wMDAwMDA='};var a=document.createElement('script');a.nonce='';a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();</script></body> </html>

CINXE.COM

Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer