CINXE.COM
<!DOCTYPE html><html lang="en"><head><title data-react-helmet="true">Role of IL-17 in Glioma Progression</title> <meta data-react-helmet="true" name="viewport" content="width=device-width, initial-scale=1, maximum-scale=5, viewport-fit=cover"/><meta data-react-helmet="true" property="og:site_name" content="scite.ai"/><meta data-react-helmet="true" property="og:type" content="website"/><meta data-react-helmet="true" property="twitter:card" content="summary_large_image"/><meta data-react-helmet="true" name="twitter:site" content="@scite"/><meta data-react-helmet="true" property="title" content="Role of IL-17 in Glioma Progression"/><meta data-react-helmet="true" property="og:title" content="Role of IL-17 in Glioma Progression"/><meta data-react-helmet="true" property="twitter:title" content="Role of IL-17 in Glioma Progression"/><meta data-react-helmet="true" property="og:image" content="http://image.thum.io/get/ogImage/https://scite.ai/reports/role-of-il-17-in-glioma-lpAzGE?bannerClosed=true&onboardingOff=true&paywallOff=true&v=2"/><meta data-react-helmet="true" property="twitter:image" content="http://image.thum.io/get/ogImage/https://scite.ai/reports/role-of-il-17-in-glioma-lpAzGE?bannerClosed=true&onboardingOff=true&paywallOff=true&v=2"/><meta data-react-helmet="true" name="description" content="Supporting: 1, Mentioning: 22 - There is increasing evidence in the literature pointing to an important role of inflammation during initiation and progression of cancer. Glioblastoma is the most common malignant primary brain tumor with approximately 23,000 newly-diagnosed cases each year in the United States, and has a dismal median survival of only 15 months. Although the blood-brain barrier maintains an immune-privileged status of the brain under steady state, intracranial tumors including gliomas are invariably infiltrated with various types of immune cells. The T helper 17 (Th17) cells, a recently discovered interleukin (IL)-17-producing T cell subtype, have been reported in several extracranial and some intracranial tumors, where they have been implicated in either pro- or antitumor activity depending on the tumor type. Here, we present a succinct review of the current literature on the prevalence and potential role of IL-17 in malignant gliomas. Further mechanistic studies on IL-17 mediated inflammatory pathway in gliomas may provide with opportunities for novel immunotherapeutic interventions."/><meta data-react-helmet="true" property="og:description" content="Supporting: 1, Mentioning: 22 - There is increasing evidence in the literature pointing to an important role of inflammation during initiation and progression of cancer. Glioblastoma is the most common malignant primary brain tumor with approximately 23,000 newly-diagnosed cases each year in the United States, and has a dismal median survival of only 15 months. Although the blood-brain barrier maintains an immune-privileged status of the brain under steady state, intracranial tumors including gliomas are invariably infiltrated with various types of immune cells. The T helper 17 (Th17) cells, a recently discovered interleukin (IL)-17-producing T cell subtype, have been reported in several extracranial and some intracranial tumors, where they have been implicated in either pro- or antitumor activity depending on the tumor type. Here, we present a succinct review of the current literature on the prevalence and potential role of IL-17 in malignant gliomas. Further mechanistic studies on IL-17 mediated inflammatory pathway in gliomas may provide with opportunities for novel immunotherapeutic interventions."/><meta data-react-helmet="true" property="twitter:description" content="Supporting: 1, Mentioning: 22 - There is increasing evidence in the literature pointing to an important role of inflammation during initiation and progression of cancer. Glioblastoma is the most common malignant primary brain tumor with approximately 23,000 newly-diagnosed cases each year in the United States, and has a dismal median survival of only 15 months. Although the blood-brain barrier maintains an immune-privileged status of the brain under steady state, intracranial tumors including gliomas are invariably infiltrated with various types of immune cells. The T helper 17 (Th17) cells, a recently discovered interleukin (IL)-17-producing T cell subtype, have been reported in several extracranial and some intracranial tumors, where they have been implicated in either pro- or antitumor activity depending on the tumor type. Here, we present a succinct review of the current literature on the prevalence and potential role of IL-17 in malignant gliomas. Further mechanistic studies on IL-17 mediated inflammatory pathway in gliomas may provide with opportunities for novel immunotherapeutic interventions."/><meta data-react-helmet="true" property="og:url" content="https://scite.ai/reports/role-of-il-17-in-glioma-lpAzGE"/><meta data-react-helmet="true" name="citation_title" content="Role of IL-17 in Glioma Progression"/><meta data-react-helmet="true" name="citation_doi" content="10.4172/2325-9701.s1-004"/><meta data-react-helmet="true" name="citation_author" content="Parajuli, Prahlad"/><meta data-react-helmet="true" name="citation_author" content="Mittal, Sandeep"/><meta data-react-helmet="true" name="citation_year" content="2013"/><meta data-react-helmet="true" name="citation_journal_title" content="Journal of Spine &Amp; Neurosurgery"/><meta data-react-helmet="true" name="citation_volume" content/><meta data-react-helmet="true" name="citation_issue" content/><meta data-react-helmet="true" name="citation_abstract" content="There is increasing evidence in the literature pointing to an important role of inflammation during initiation and progression of cancer. Glioblastoma is the most common malignant primary brain tumor with approximately 23,000 newly-diagnosed cases each year in the United States, and has a dismal median survival of only 15 months. Although the blood-brain barrier maintains an immune-privileged status of the brain under steady state, intracranial tumors including gliomas are invariably infiltrated with various types of immune cells. The T helper 17 (Th17) cells, a recently discovered interleukin (IL)-17-producing T cell subtype, have been reported in several extracranial and some intracranial tumors, where they have been implicated in either pro- or antitumor activity depending on the tumor type. Here, we present a succinct review of the current literature on the prevalence and potential role of IL-17 in malignant gliomas. Further mechanistic studies on IL-17 mediated inflammatory pathway in gliomas may provide with opportunities for novel immunotherapeutic interventions."/><meta data-react-helmet="true" name="citation_public_url" content="https://doi.org/10.4172/2325-9701.s1-004"/> <link data-react-helmet="true" rel="preconnect" href="https://cdn.scite.ai" crossorigin="true"/><link data-react-helmet="true" rel="preconnect" href="https://fonts.googleapis.com"/><link data-react-helmet="true" rel="preconnect" href="https://fonts.gstatic.com" crossorigin="true"/><link data-react-helmet="true" rel="shortcut icon" href="https://cdn.scite.ai/assets/images/favicon.ico"/><link data-react-helmet="true" rel="stylesheet preload prefetch" as="style" href="https://cdn.scite.ai/assets/css/line-awesome-font-awesome.min.css?v=2"/><link data-react-helmet="true" rel="preload" as="style" href="https://fonts.googleapis.com/css2?family=IBM+Plex+Sans:wght@200;300;400;500;600&display=swap"/><link data-react-helmet="true" rel="stylesheet" as="style" href="https://fonts.googleapis.com/css2?family=IBM+Plex+Sans:wght@200;300;400;500;600&display=swap" media="print" onload="this.media='all'"/><link data-react-helmet="true" rel="canonical" href="https://scite.ai/reports/role-of-il-17-in-glioma-lpAzGE"/> <script data-react-helmet="true" src="https://www.recaptcha.net/recaptcha/api.js?render=6LcnMGsqAAAAAJLHdGuust5QwzLk-asKPW5MWbAx"></script><script data-react-helmet="true" type="application/ld+json">{"@context":"http://schema.org","@graph":[{"@id":"#issue","@type":"PublicationIssue","datePublished":2013,"isPartOf":{"@id":"#periodical","@type":["PublicationVolume","Periodical"],"name":"Journal of Spine &Amp; Neurosurgery","issn":["2325-9701"],"publisher":"OMICS Publishing Group"}},{"@type":"ScholarlyArticle","isPartOf":"#issue","description":"There is increasing evidence in the literature pointing to an important role of inflammation during initiation and progression of cancer. Glioblastoma is the most common malignant primary brain tumor with approximately 23,000 newly-diagnosed cases each year in the United States, and has a dismal median survival of only 15 months. Although the blood-brain barrier maintains an immune-privileged status of the brain under steady state, intracranial tumors including gliomas are invariably infiltrated with various types of immune cells. The T helper 17 (Th17) cells, a recently discovered interleukin (IL)-17-producing T cell subtype, have been reported in several extracranial and some intracranial tumors, where they have been implicated in either pro- or antitumor activity depending on the tumor type. Here, we present a succinct review of the current literature on the prevalence and potential role of IL-17 in malignant gliomas. Further mechanistic studies on IL-17 mediated inflammatory pathway in gliomas may provide with opportunities for novel immunotherapeutic interventions.","abstract":"There is increasing evidence in the literature pointing to an important role of inflammation during initiation and progression of cancer. Glioblastoma is the most common malignant primary brain tumor with approximately 23,000 newly-diagnosed cases each year in the United States, and has a dismal median survival of only 15 months. Although the blood-brain barrier maintains an immune-privileged status of the brain under steady state, intracranial tumors including gliomas are invariably infiltrated with various types of immune cells. The T helper 17 (Th17) cells, a recently discovered interleukin (IL)-17-producing T cell subtype, have been reported in several extracranial and some intracranial tumors, where they have been implicated in either pro- or antitumor activity depending on the tumor type. Here, we present a succinct review of the current literature on the prevalence and potential role of IL-17 in malignant gliomas. Further mechanistic studies on IL-17 mediated inflammatory pathway in gliomas may provide with opportunities for novel immunotherapeutic interventions.","sameAs":"https://doi.org/10.4172/2325-9701.s1-004","name":"Role of IL-17 in Glioma Progression","headline":"Role of IL-17 in Glioma Progression","author":["Prahlad Parajuli","Sandeep Mittal"],"publisher":{"@type":"Organization","name":"OMICS Publishing Group"},"datePublished":2013}]}</script> <link data-chunk="main" rel="stylesheet" href="https://cdn.scite.ai/assets/dist/main.2a4a881c9257077826c8.css"> <link data-chunk="Report" rel="stylesheet" href="https://cdn.scite.ai/assets/dist/6901.00ffb5a62514ad11206f.css"> <link data-chunk="Report" rel="stylesheet" href="https://cdn.scite.ai/assets/dist/6392.ee3f7fe674ceac954f77.css"> </head> <body><div id="scite-app"><!--$--><div class="ReportApp__layout___ljMuO"><div><nav class="NavBar__navBarContainer___skQfv"><div class="NavBar__navBar___ELwVq NavBar__notStatic___bzily" style="transform:translate3d(0,0%,0)"><div class="NavBar__navContents___X2u7r"><a class="NavBar__logo___aYKoi" href="/"><img alt="scite logo" width="115px" height="38px" class="NavBar__logoDesktop___Cwo_2" style="filter:contrast(2.15)" src="https://cdn.scite.ai/assets/images/logo-blue.svg"/><img alt="scite logo" width="64px" height="38px" class="NavBar__logoMobile___dA77Y" style="filter:contrast(2.15)" src="https://cdn.scite.ai/assets/images/logo-blue.svg"/></a><form class="SearchInput__searchInput___ze14_ NavBar__searchBox___l1QGV NavBar__searchBarBorder___xB_jN SearchBox__input___Q1BdB"><div></div><input aria-label="search" data-showdropdown="true" autoComplete="off" class="SearchInput__input___D08BX" type="text" placeholder="Search by title, author, keywords or DOI" value=""/><div class="SearchInput__button___L2ljx NavBar__searchButton___ZfbtP" aria-label="search-button" role="button" tabindex="0"><i class="icon icon-search SearchInput__icon___sEZb9"></i></div></form><i class="NavBar__mobileSearchIcon___Ftzic icon icon-search" role="button" tabindex="0" aria-label="Search"></i><div class="NavBar__rightContent___bJvfl"><div class="NavBar__navButtonsLayout___SnYwi"><div class="NavButtons__navButtons___uY5SG"><div class="NavButtons__mobileHide___bSlk6"><div class="HoverLink__container___PEeZm"><a class="HoverLink__link___wZgvn Link__link___plGt2 HoverLink__link___wZgvn" tabindex="0" role="button" href="/assistant">Assistant</a></div><div><div class="HoverLink__container___PEeZm"><a class="HoverLink__link___wZgvn Link__link___plGt2 HoverLink__link___wZgvn" tabindex="0" role="button">Product<div class="OpenerIcon__folder___jiKx6 false HoverLink__icon___H8E9g"><i class="OpenerIcon__angleDown___QHC0i icon icon-down-carret"></i></div></a></div></div><div><div class="HoverLink__container___PEeZm"><a class="HoverLink__link___wZgvn Link__link___plGt2 HoverLink__link___wZgvn" tabindex="0" role="button">Solutions<div class="OpenerIcon__folder___jiKx6 false HoverLink__icon___H8E9g"><i class="OpenerIcon__angleDown___QHC0i icon icon-down-carret"></i></div></a></div></div><div class="HoverLink__container___PEeZm"><a class="HoverLink__link___wZgvn Link__link___plGt2 HoverLink__link___wZgvn" tabindex="0" role="button" href="/pricing">Pricing</a></div><div class="HoverLink__container___PEeZm"><a class="HoverLink__link___wZgvn Link__link___plGt2 HoverLink__link___wZgvn" tabindex="0" role="button" href="/blog">Blog</a></div></div></div></div></div></div></div></nav><div><nav class="NavBar__navBarContainer___skQfv NavBar__spacer___BOOCE" style="visibility:hidden"><div class="NavBar__navBar___ELwVq NavBar__notStatic___bzily NavBar__spacer___BOOCE" style="transform:translate3d(0,0%,0)"><div class="NavBar__navContents___X2u7r"><a class="NavBar__logo___aYKoi" href="/"><img alt="scite logo" width="115px" height="38px" class="NavBar__logoDesktop___Cwo_2" style="filter:contrast(2.15)" src="https://cdn.scite.ai/assets/images/logo-blue.svg"/><img alt="scite logo" width="64px" height="38px" class="NavBar__logoMobile___dA77Y" style="filter:contrast(2.15)" src="https://cdn.scite.ai/assets/images/logo-blue.svg"/></a><form class="SearchInput__searchInput___ze14_ NavBar__searchBox___l1QGV NavBar__searchBarBorder___xB_jN SearchBox__input___Q1BdB"><div></div><input aria-label="search" data-showdropdown="true" autoComplete="off" class="SearchInput__input___D08BX" type="text" placeholder="Search by title, author, keywords or DOI" value=""/><div class="SearchInput__button___L2ljx NavBar__searchButton___ZfbtP" aria-label="search-button" role="button" tabindex="0"><i class="icon icon-search SearchInput__icon___sEZb9"></i></div></form><i class="NavBar__mobileSearchIcon___Ftzic icon icon-search" role="button" tabindex="0" aria-label="Search"></i><div class="NavBar__rightContent___bJvfl"><div class="NavBar__navButtonsLayout___SnYwi"><div class="NavButtons__navButtons___uY5SG"><div class="NavButtons__mobileHide___bSlk6"><div class="HoverLink__container___PEeZm"><a class="HoverLink__link___wZgvn Link__link___plGt2 HoverLink__link___wZgvn" tabindex="0" role="button" href="/assistant">Assistant</a></div><div><div class="HoverLink__container___PEeZm"><a class="HoverLink__link___wZgvn Link__link___plGt2 HoverLink__link___wZgvn" tabindex="0" role="button">Product<div class="OpenerIcon__folder___jiKx6 false HoverLink__icon___H8E9g"><i class="OpenerIcon__angleDown___QHC0i icon icon-down-carret"></i></div></a></div></div><div><div class="HoverLink__container___PEeZm"><a class="HoverLink__link___wZgvn Link__link___plGt2 HoverLink__link___wZgvn" tabindex="0" role="button">Solutions<div class="OpenerIcon__folder___jiKx6 false HoverLink__icon___H8E9g"><i class="OpenerIcon__angleDown___QHC0i icon icon-down-carret"></i></div></a></div></div><div class="HoverLink__container___PEeZm"><a class="HoverLink__link___wZgvn Link__link___plGt2 HoverLink__link___wZgvn" tabindex="0" role="button" href="/pricing">Pricing</a></div><div class="HoverLink__container___PEeZm"><a class="HoverLink__link___wZgvn Link__link___plGt2 HoverLink__link___wZgvn" tabindex="0" role="button" href="/blog">Blog</a></div></div></div></div></div></div></div></nav></div></div><div class="ReportApp__app___hkfPJ"><div><div class="ReportPanel__reportHeader___TyrUa"><div class="ReportPanel__leftCol___rZCkG"><div class="TitlePaper__titlePaper___qfYlK"><span class="Reference__reference___AIzFu"><span><span class="Badge__pill___QnwOm Reference__journalBadge___m3cAs"><div class="Tooltip__reference___hgPSY"><span><a class="Link__link___plGt2" tabindex="0" href="/journals/journal-of-spine-neurosurgery-ZGp0p">J Spine Neurosurg</a></span></div></span><span class="Reference__pubYear___BW5ev"> <!-- -->2013<!-- --> </span><div class="Reference__doiContainer___kZXiq"><span>DOI: <!-- -->10.4172/2325-9701.s1-004</span><div class="Reference__tooltip___Nu3gD Tooltip__reference___hgPSY"><i class="copy fa fa-copy fa-lg"></i></div><span> |</span><a class="Reference__fullTextLink___p92ic Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Reference__fullTextLink___p92ic" href="https://doi.org/10.4172/2325-9701.s1-004" tabindex="0" role="link" target="_blank" rel="noopener noreferrer nofollow">View full text</a><span> |</span><a class="Reference__fullTextLink___p92ic Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Reference__fullTextLink___p92ic" tabindex="0" role="button">Cite</a></div></span></span><div class="TitlePaper__widgetContainer___xNQUF"><div class="TitlePaper__delimiter___FdQmc">|</div><div class="Notification__notificationContainer___N06uS " style="opacity:1;pointer-events:auto"><div role="button" class="Notification__notification___rIkeZ" tabindex="0"><div class="Notification__bellIcon___IKprf fa fa-bell"></div><div class="Notification__tooltip___DjoOa Tooltip__reference___hgPSY"><span class="Notification__setNotification___dsjeh">Sign up to set email alerts</span></div></div></div><span> |</span><div class="SharingWidget__container___UnD9v"><a class="SocialIcon__socialIcon___gm1fE SharingWidget__icon___Rek8d Link__link___plGt2 SocialIcon__socialIcon___gm1fE SharingWidget__icon___Rek8d" href="https://twitter.com/intent/tweet?text=scite%20Report%20-%20Role%20of%20IL-17%20in%20Glioma%20Progression&url=" tabindex="0" role="link" target="_blank" rel="noopener noreferrer" aria-label="https://twitter.com/scite"><i class="icon icon-twitter-new"></i></a><a class="SocialIcon__socialIcon___gm1fE SharingWidget__icon___Rek8d Link__link___plGt2 SocialIcon__socialIcon___gm1fE SharingWidget__icon___Rek8d" href="https://www.facebook.com/sharer/sharer.php?u=" tabindex="0" role="link" target="_blank" rel="noopener noreferrer" aria-label="https://facebook.com/sciteai"><i class="icon icon-facebook-new"></i></a><a class="SocialIcon__socialIcon___gm1fE SharingWidget__icon___Rek8d Link__link___plGt2 SocialIcon__socialIcon___gm1fE SharingWidget__icon___Rek8d" href="https://www.linkedin.com/sharing/share-offsite/?url=" tabindex="0" role="link" target="_blank" rel="noopener noreferrer" aria-label="https://www.linkedin.com/company/sciteai/"><i class="icon icon-linkedin-new"></i></a></div></div><div class="TitlePaper__paperTitle___zucih"><span><h1 class="Header__h1___YjMd5 TitlePaper__paperTitleHeader___p1alj">Role of IL-17 in Glioma Progression</h1></span></div><div class="Authors__authors___uWMEz"><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/prahlad-parajuli-5Gl4gV"><span>Prahlad Parajuli</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/karmanos-cancer-institute-G5z6L">1</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/sandeep-mittal-8GXGxY"><span>Sandeep Mittal</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/karmanos-cancer-institute-G5z6L">2</a></sup></div><span> </span></div></div><div class="TitlePaper__abstractWrapper___S7D_F"><span><h2 class="Header__h2___MuBOH TitlePaper__abstract___GrSZl"><strong>Abstract:</strong> <!-- --> <!-- --> <span>There is increasing evidence in the literature pointing to an important role of inflammation during initiation and progression of cancer. Glioblastoma is the most common malignant primary brain tumor with approximately 23,000 newly-diagnosed cases each year in the United States, and has a dismal median survival of only 15 months. Although the blood-brain barrier maintains an immune-privileged status of the brain under steady state, intracranial tumors including gliomas are invariably infiltrated with various t…</span><span class="TitlePaper__expandAbstract___O_45M" role="button" tabindex="0"> <!-- --> <!-- -->Show more</span></h2></span></div><a class="TitlePaper__helpMeCta___oNbp1 Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j TitlePaper__helpMeCta___oNbp1" tabindex="0" role="button">Help me understand this report</a></div></div><div class="ReportDropdown__dropdownMenuContainer___G8S6M"><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div><div><div class="ReportPanel__mainLayout___kuDP5"><div class="ReportPanel__filtersLayout___KAxUi"><div class="Filters__filters___FcFPI"><div class="Filters__loadingLayout___i7nI3" style="opacity:0;pointer-events:auto"><div data-testid="circle-spinner" class="CircleSpinner__sciteLoadingRing___nlTrH" style="width:80px;height:80px"><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div></div></div><div style="opacity:0;pointer-events:none"><div class="FilterCard__filterCard___bZEVP"><div class="FilterCard__noInput___lsgWM"><div class="FilterCard__filterCardHeader___puB2k" role="button" tabindex="0" aria-label="Expand Search citation statements"><p class="FilterCard__header___dRl1u Paragraph__body____m5FY Paragraph__bold___PhFOq">Search citation statements<!-- --> </p></div><div class="SearchCites__layout___vB255"><form class="SearchInput__searchInput___ze14_ SearchCites__search___Y_Yhp"><input aria-label="search citations" data-showdropdown="true" autoComplete="off" class="SearchInput__input___D08BX SearchCites__input___dC99x" type="text" placeholder="Context, author(s), title etc." value=""/><div class="SearchInput__button___L2ljx" aria-label="search-button" role="button" tabindex="0"><i class="icon icon-search SearchInput__icon___sEZb9"></i></div></form></div><div class="Filters__sortBox___WYNFN"><style data-emotion="css b62m3t-container">.css-b62m3t-container{position:relative;box-sizing:border-box;}</style><div class=" css-b62m3t-container"><style data-emotion="css 7pg0cj-a11yText">.css-7pg0cj-a11yText{z-index:9999;border:0;clip:rect(1px, 1px, 1px, 1px);height:1px;width:1px;position:absolute;overflow:hidden;padding:0;white-space:nowrap;}</style><span id="react-select-292781-live-region" class="css-7pg0cj-a11yText"></span><span aria-live="polite" aria-atomic="false" aria-relevant="additions text" class="css-7pg0cj-a11yText"></span><style data-emotion="css 1vom5ua-control">.css-1vom5ua-control{-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;cursor:default;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-box-flex-wrap:wrap;-webkit-flex-wrap:wrap;-ms-flex-wrap:wrap;flex-wrap:wrap;-webkit-box-pack:justify;-webkit-justify-content:space-between;justify-content:space-between;min-height:38px;outline:0!important;position:relative;-webkit-transition:all 100ms;transition:all 100ms;background-color:hsl(0, 0%, 100%);border-color:hsl(0, 0%, 80%);border-radius:12px;border-style:solid;border-width:1px;box-sizing:border-box;}.css-1vom5ua-control:hover{border-color:hsl(0, 0%, 70%);}</style><div class=" css-1vom5ua-control"><style data-emotion="css hlgwow">.css-hlgwow{-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;display:grid;-webkit-flex:1;-ms-flex:1;flex:1;-webkit-box-flex-wrap:wrap;-webkit-flex-wrap:wrap;-ms-flex-wrap:wrap;flex-wrap:wrap;-webkit-overflow-scrolling:touch;position:relative;overflow:hidden;padding:2px 8px;box-sizing:border-box;}</style><div class=" css-hlgwow"><div style="label:singleValue;grid-area:1 / 1 / 2 / 3;max-width:100%;overflow:hidden;text-overflow:ellipsis;white-space:nowrap;color:hsl(0, 0%, 20%);margin-left:2px;margin-right:2px;box-sizing:border-box">Order By: <!-- -->Relevance</div><style data-emotion="css 19bb58m">.css-19bb58m{visibility:visible;-webkit-flex:1 1 auto;-ms-flex:1 1 auto;flex:1 1 auto;display:inline-grid;grid-area:1/1/2/3;grid-template-columns:0 min-content;margin:2px;padding-bottom:2px;padding-top:2px;color:hsl(0, 0%, 20%);box-sizing:border-box;}.css-19bb58m:after{content:attr(data-value) " ";visibility:hidden;white-space:pre;grid-area:1/2;font:inherit;min-width:2px;border:0;margin:0;outline:0;padding:0;}</style><div class=" css-19bb58m" data-value=""><input class="" style="label:input;color:inherit;background:0;opacity:1;width:100%;grid-area:1 / 2;font:inherit;min-width:2px;border:0;margin:0;outline:0;padding:0" autoCapitalize="none" autoComplete="off" autoCorrect="off" id="react-select-292781-input" spellcheck="false" tabindex="0" type="text" aria-autocomplete="list" aria-expanded="false" aria-haspopup="true" role="combobox" value=""/></div></div><style data-emotion="css 1wy0on6">.css-1wy0on6{-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-align-self:stretch;-ms-flex-item-align:stretch;align-self:stretch;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-shrink:0;-ms-flex-negative:0;flex-shrink:0;box-sizing:border-box;}</style><div class=" css-1wy0on6"><span class=" css-0"></span><style data-emotion="css 1xc3v61-indicatorContainer">.css-1xc3v61-indicatorContainer{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-transition:color 150ms;transition:color 150ms;color:hsl(0, 0%, 80%);padding:8px;box-sizing:border-box;}.css-1xc3v61-indicatorContainer:hover{color:hsl(0, 0%, 60%);}</style><div class=" css-1xc3v61-indicatorContainer" aria-hidden="true"><style data-emotion="css 8mmkcg">.css-8mmkcg{display:inline-block;fill:currentColor;line-height:1;stroke:currentColor;stroke-width:0;}</style><svg height="20" width="20" viewBox="0 0 20 20" aria-hidden="true" focusable="false" class="css-8mmkcg"><path d="M4.516 7.548c0.436-0.446 1.043-0.481 1.576 0l3.908 3.747 3.908-3.747c0.533-0.481 1.141-0.446 1.574 0 0.436 0.445 0.408 1.197 0 1.615-0.406 0.418-4.695 4.502-4.695 4.502-0.217 0.223-0.502 0.335-0.787 0.335s-0.57-0.112-0.789-0.335c0 0-4.287-4.084-4.695-4.502s-0.436-1.17 0-1.615z"></path></svg></div></div></div></div></div></div></div><div class="FilterCard__filterCard___bZEVP"><div class="FilterCard__noInput___lsgWM"><div class="FilterCard__filterCardHeader___puB2k" role="button" tabindex="0" aria-label="Expand Paper Sections"><div class="FilterCard__tooltip___q395i Tooltip__reference___hgPSY"><p class="FilterCard__header___dRl1u Paragraph__body____m5FY Paragraph__bold___PhFOq">Paper Sections<!-- --> </p><i class="FilterCard__icon___iqNMr fa fa-info-circle"></i></div></div><div><style data-emotion="css b62m3t-container">.css-b62m3t-container{position:relative;box-sizing:border-box;}</style><div class=" css-b62m3t-container"><style data-emotion="css 7pg0cj-a11yText">.css-7pg0cj-a11yText{z-index:9999;border:0;clip:rect(1px, 1px, 1px, 1px);height:1px;width:1px;position:absolute;overflow:hidden;padding:0;white-space:nowrap;}</style><span id="react-select-292782-live-region" class="css-7pg0cj-a11yText"></span><span aria-live="polite" aria-atomic="false" aria-relevant="additions text" class="css-7pg0cj-a11yText"></span><style data-emotion="css 13cymwt-control">.css-13cymwt-control{-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;cursor:default;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-box-flex-wrap:wrap;-webkit-flex-wrap:wrap;-ms-flex-wrap:wrap;flex-wrap:wrap;-webkit-box-pack:justify;-webkit-justify-content:space-between;justify-content:space-between;min-height:38px;outline:0!important;position:relative;-webkit-transition:all 100ms;transition:all 100ms;background-color:hsl(0, 0%, 100%);border-color:hsl(0, 0%, 80%);border-radius:4px;border-style:solid;border-width:1px;box-sizing:border-box;}.css-13cymwt-control:hover{border-color:hsl(0, 0%, 70%);}</style><div class=" css-13cymwt-control"><style data-emotion="css hlgwow">.css-hlgwow{-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;display:grid;-webkit-flex:1;-ms-flex:1;flex:1;-webkit-box-flex-wrap:wrap;-webkit-flex-wrap:wrap;-ms-flex-wrap:wrap;flex-wrap:wrap;-webkit-overflow-scrolling:touch;position:relative;overflow:hidden;padding:2px 8px;box-sizing:border-box;}</style><div class=" css-hlgwow"><style data-emotion="css 1jqq78o-placeholder">.css-1jqq78o-placeholder{grid-area:1/1/2/3;color:hsl(0, 0%, 50%);margin-left:2px;margin-right:2px;box-sizing:border-box;}</style><div class=" css-1jqq78o-placeholder" id="react-select-292782-placeholder">Select...</div><style data-emotion="css 19bb58m">.css-19bb58m{visibility:visible;-webkit-flex:1 1 auto;-ms-flex:1 1 auto;flex:1 1 auto;display:inline-grid;grid-area:1/1/2/3;grid-template-columns:0 min-content;margin:2px;padding-bottom:2px;padding-top:2px;color:hsl(0, 0%, 20%);box-sizing:border-box;}.css-19bb58m:after{content:attr(data-value) " ";visibility:hidden;white-space:pre;grid-area:1/2;font:inherit;min-width:2px;border:0;margin:0;outline:0;padding:0;}</style><div class=" css-19bb58m" data-value=""><input class="" style="label:input;color:inherit;background:0;opacity:1;width:100%;grid-area:1 / 2;font:inherit;min-width:2px;border:0;margin:0;outline:0;padding:0" autoCapitalize="none" autoComplete="off" autoCorrect="off" id="react-select-292782-input" spellcheck="false" tabindex="0" type="text" aria-autocomplete="list" aria-expanded="false" aria-haspopup="true" role="combobox" aria-describedby="react-select-292782-placeholder" value=""/></div></div><style data-emotion="css 1wy0on6">.css-1wy0on6{-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-align-self:stretch;-ms-flex-item-align:stretch;align-self:stretch;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-shrink:0;-ms-flex-negative:0;flex-shrink:0;box-sizing:border-box;}</style><div class=" css-1wy0on6"><style data-emotion="css 1u9des2-indicatorSeparator">.css-1u9des2-indicatorSeparator{-webkit-align-self:stretch;-ms-flex-item-align:stretch;align-self:stretch;width:1px;background-color:hsl(0, 0%, 80%);margin-bottom:8px;margin-top:8px;box-sizing:border-box;}</style><span class=" css-1u9des2-indicatorSeparator"></span><style data-emotion="css 1xc3v61-indicatorContainer">.css-1xc3v61-indicatorContainer{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-transition:color 150ms;transition:color 150ms;color:hsl(0, 0%, 80%);padding:8px;box-sizing:border-box;}.css-1xc3v61-indicatorContainer:hover{color:hsl(0, 0%, 60%);}</style><div class=" css-1xc3v61-indicatorContainer" aria-hidden="true"><style data-emotion="css 8mmkcg">.css-8mmkcg{display:inline-block;fill:currentColor;line-height:1;stroke:currentColor;stroke-width:0;}</style><svg height="20" width="20" viewBox="0 0 20 20" aria-hidden="true" focusable="false" class="css-8mmkcg"><path d="M4.516 7.548c0.436-0.446 1.043-0.481 1.576 0l3.908 3.747 3.908-3.747c0.533-0.481 1.141-0.446 1.574 0 0.436 0.445 0.408 1.197 0 1.615-0.406 0.418-4.695 4.502-4.695 4.502-0.217 0.223-0.502 0.335-0.787 0.335s-0.57-0.112-0.789-0.335c0 0-4.287-4.084-4.695-4.502s-0.436-1.17 0-1.615z"></path></svg></div></div></div></div><div class="CheckRowCount__sectionRow___vyiE6"><label class="CheckRow__checkRow___Wumpa"><input class="fa fa-lg fa-check Checkbox__checkbox___dGd5x " type="checkbox"/><span class="CheckRow__checkRowLabel___ax_ST">Discussion</span></label><span><span>4</span></span></div><div class="CheckRowCount__sectionRow___vyiE6"><label class="CheckRow__checkRow___Wumpa"><input class="fa fa-lg fa-check Checkbox__checkbox___dGd5x " type="checkbox"/><span class="CheckRow__checkRowLabel___ax_ST">Anakinra Reduced Inflammatory Signaling In Lymphocytes Co-cu</span></label><span><span>1</span></span></div></div></div></div><div class="FilterCard__filterCard___bZEVP"><div class="FilterCard__noInput___lsgWM"><div class="FilterCard__filterCardHeader___puB2k" role="button" tabindex="0" aria-label="Expand Citation Types"><div class="FilterCard__tooltip___q395i Tooltip__reference___hgPSY"><p class="FilterCard__header___dRl1u Paragraph__body____m5FY Paragraph__bold___PhFOq">Citation Types<!-- --> </p><i class="FilterCard__icon___iqNMr fa fa-info-circle"></i></div></div><div class=""><div class="Classification__row___s1V6w"><div class="Classification__rowLeft___VoLlX"><label class="CheckRow__checkRow___Wumpa"><input class="fa fa-lg fa-check Checkbox__checkbox___dGd5x " type="checkbox"/><span class="CheckRow__checkRowLabel___ax_ST">Supporting</span></label><div class="Classification__rowType___282g8"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i></div></div><div class="Classification__rowRight___Zxitp"><span class="Classification__count___Y86vw">1</span></div></div><div class="Classification__row___s1V6w"><div class="Classification__rowLeft___VoLlX"><label class="CheckRow__checkRow___Wumpa"><input class="fa fa-lg fa-check Checkbox__checkbox___dGd5x " type="checkbox"/><span class="CheckRow__checkRowLabel___ax_ST">Mentioning</span></label><div class="Classification__rowType___282g8"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i></div></div><div class="Classification__rowRight___Zxitp"><span class="Classification__count___Y86vw">22</span></div></div><div class="Classification__row___s1V6w"><div class="Classification__rowLeft___VoLlX"><label class="CheckRow__checkRow___Wumpa"><input class="fa fa-lg fa-check Checkbox__checkbox___dGd5x " type="checkbox"/><span class="CheckRow__checkRowLabel___ax_ST">Contrasting</span></label><div class="Classification__rowType___282g8"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i></div></div><div class="Classification__rowRight___Zxitp"><span class="Classification__count___Y86vw">0</span></div></div></div></div></div><div class="FilterCard__filterCard___bZEVP"><div class="FilterCard__noInput___lsgWM"><div class="FilterCard__filterCardHeader___puB2k" role="button" tabindex="0" aria-label="Expand Year Published"><p class="FilterCard__header___dRl1u Paragraph__body____m5FY Paragraph__bold___PhFOq">Year Published<!-- --> </p></div><div class="Filters__yearRange___mtpTm"><div class="CitationsYearBarChart__barChartContainer___fOCtc"><div class="CitationsYearBarChart__barChart___J1Zgl"><div class="CitationsYearBarChart__bar___QB0KQ" style="width:16.666666666666668%"><div class="CitationsYearBarChart__barContainer___A2gcx Tooltip__reference___hgPSY"><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__supporting___iMyv8" style="height:NaNrem"></div><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__contradicting___ZRgkC" style="height:NaNrem"></div><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__mentioning___rfif5" style="height:4.8rem"></div></div></div><div class="CitationsYearBarChart__bar___QB0KQ" style="width:50%"><div class="CitationsYearBarChart__barContainer___A2gcx Tooltip__reference___hgPSY"><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__supporting___iMyv8" style="height:NaNrem"></div><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__contradicting___ZRgkC" style="height:NaNrem"></div><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__mentioning___rfif5" style="height:0rem"></div></div></div><div class="CitationsYearBarChart__bar___QB0KQ" style="width:16.666666666666668%"><div class="CitationsYearBarChart__barContainer___A2gcx Tooltip__reference___hgPSY"><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__supporting___iMyv8" style="height:NaNrem"></div><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__contradicting___ZRgkC" style="height:NaNrem"></div><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__mentioning___rfif5" style="height:3.8039100017307743rem"></div></div></div><div class="CitationsYearBarChart__bar___QB0KQ" style="width:16.666666666666668%"><div class="CitationsYearBarChart__barContainer___A2gcx Tooltip__reference___hgPSY"><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__supporting___iMyv8" style="height:NaNrem"></div><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__contradicting___ZRgkC" style="height:NaNrem"></div><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__mentioning___rfif5" style="height:2.4rem"></div></div></div><div class="CitationsYearBarChart__bar___QB0KQ" style="width:16.666666666666668%"><div class="CitationsYearBarChart__barContainer___A2gcx Tooltip__reference___hgPSY"><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__supporting___iMyv8" style="height:NaNrem"></div><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__contradicting___ZRgkC" style="height:NaNrem"></div><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__mentioning___rfif5" style="height:4.8rem"></div></div></div><div class="CitationsYearBarChart__bar___QB0KQ" style="width:16.666666666666668%"><div class="CitationsYearBarChart__barContainer___A2gcx Tooltip__reference___hgPSY"><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__supporting___iMyv8" style="height:NaNrem"></div><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__contradicting___ZRgkC" style="height:NaNrem"></div><div class="CitationsYearBarChart__barPart___aKZ37 CitationsYearBarChart__mentioning___rfif5" style="height:2.4rem"></div></div></div></div></div><div><div aria-disabled="false" class="undefined InputRangeFilter__range___i8qUt"><span class="InputRangeFilter__hide___cvWG2 input-range__label--min"><span class="input-range__label-container InputRangeFilter__labelContainer___UOzQG">2016</span></span><div class="InputRangeFilter__track___Fdwrd input-range__track--background"><div style="left:0%;width:100%" class="InputRangeFilter__track___Fdwrd InputRangeFilter__activeTrack___Xb3wK"></div><span class="input-range__slider-container" style="position:absolute;left:0%"><span class="InputRangeFilter__label___uyn35 InputRangeFilter__labelValue___vCEiN InputRangeFilter__labelBottom___LxO3k"><span class="input-range__label-container InputRangeFilter__labelContainer___UOzQG">2016</span></span><div aria-valuemax="2023" aria-valuemin="2016" aria-valuenow="2016" class="InputRangeFilter__slider___CpeJ9" draggable="false" role="slider" tabindex="0"></div></span><span class="input-range__slider-container" style="position:absolute;left:100%"><span class="InputRangeFilter__label___uyn35 InputRangeFilter__labelValue___vCEiN InputRangeFilter__labelBottom___LxO3k"><span class="input-range__label-container InputRangeFilter__labelContainer___UOzQG">2023</span></span><div aria-valuemax="2023" aria-valuemin="2016" aria-valuenow="2023" class="InputRangeFilter__slider___CpeJ9" draggable="false" role="slider" tabindex="0"></div></span></div><span class="InputRangeFilter__hide___cvWG2 input-range__label--max"><span class="input-range__label-container InputRangeFilter__labelContainer___UOzQG">2023</span></span></div></div></div></div></div><div class="FilterCard__filterCard___bZEVP"><div class="FilterCard__noInput___lsgWM"><div class="FilterCard__filterCardHeader___puB2k" role="button" tabindex="0" aria-label="Expand Publication Types"><p class="FilterCard__header___dRl1u Paragraph__body____m5FY Paragraph__bold___PhFOq">Publication Types<!-- --> </p></div><div><style data-emotion="css b62m3t-container">.css-b62m3t-container{position:relative;box-sizing:border-box;}</style><div class=" css-b62m3t-container"><style data-emotion="css 7pg0cj-a11yText">.css-7pg0cj-a11yText{z-index:9999;border:0;clip:rect(1px, 1px, 1px, 1px);height:1px;width:1px;position:absolute;overflow:hidden;padding:0;white-space:nowrap;}</style><span id="react-select-292783-live-region" class="css-7pg0cj-a11yText"></span><span aria-live="polite" aria-atomic="false" aria-relevant="additions text" class="css-7pg0cj-a11yText"></span><style data-emotion="css 13cymwt-control">.css-13cymwt-control{-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;cursor:default;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-box-flex-wrap:wrap;-webkit-flex-wrap:wrap;-ms-flex-wrap:wrap;flex-wrap:wrap;-webkit-box-pack:justify;-webkit-justify-content:space-between;justify-content:space-between;min-height:38px;outline:0!important;position:relative;-webkit-transition:all 100ms;transition:all 100ms;background-color:hsl(0, 0%, 100%);border-color:hsl(0, 0%, 80%);border-radius:4px;border-style:solid;border-width:1px;box-sizing:border-box;}.css-13cymwt-control:hover{border-color:hsl(0, 0%, 70%);}</style><div class=" css-13cymwt-control"><style data-emotion="css hlgwow">.css-hlgwow{-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;display:grid;-webkit-flex:1;-ms-flex:1;flex:1;-webkit-box-flex-wrap:wrap;-webkit-flex-wrap:wrap;-ms-flex-wrap:wrap;flex-wrap:wrap;-webkit-overflow-scrolling:touch;position:relative;overflow:hidden;padding:2px 8px;box-sizing:border-box;}</style><div class=" css-hlgwow"><style data-emotion="css 1jqq78o-placeholder">.css-1jqq78o-placeholder{grid-area:1/1/2/3;color:hsl(0, 0%, 50%);margin-left:2px;margin-right:2px;box-sizing:border-box;}</style><div class=" css-1jqq78o-placeholder" id="react-select-292783-placeholder">Select...</div><style data-emotion="css 19bb58m">.css-19bb58m{visibility:visible;-webkit-flex:1 1 auto;-ms-flex:1 1 auto;flex:1 1 auto;display:inline-grid;grid-area:1/1/2/3;grid-template-columns:0 min-content;margin:2px;padding-bottom:2px;padding-top:2px;color:hsl(0, 0%, 20%);box-sizing:border-box;}.css-19bb58m:after{content:attr(data-value) " ";visibility:hidden;white-space:pre;grid-area:1/2;font:inherit;min-width:2px;border:0;margin:0;outline:0;padding:0;}</style><div class=" css-19bb58m" data-value=""><input class="" style="label:input;color:inherit;background:0;opacity:1;width:100%;grid-area:1 / 2;font:inherit;min-width:2px;border:0;margin:0;outline:0;padding:0" autoCapitalize="none" autoComplete="off" autoCorrect="off" id="react-select-292783-input" spellcheck="false" tabindex="0" type="text" aria-autocomplete="list" aria-expanded="false" aria-haspopup="true" role="combobox" aria-describedby="react-select-292783-placeholder" value=""/></div></div><style data-emotion="css 1wy0on6">.css-1wy0on6{-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-align-self:stretch;-ms-flex-item-align:stretch;align-self:stretch;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-shrink:0;-ms-flex-negative:0;flex-shrink:0;box-sizing:border-box;}</style><div class=" css-1wy0on6"><style data-emotion="css 1u9des2-indicatorSeparator">.css-1u9des2-indicatorSeparator{-webkit-align-self:stretch;-ms-flex-item-align:stretch;align-self:stretch;width:1px;background-color:hsl(0, 0%, 80%);margin-bottom:8px;margin-top:8px;box-sizing:border-box;}</style><span class=" css-1u9des2-indicatorSeparator"></span><style data-emotion="css 1xc3v61-indicatorContainer">.css-1xc3v61-indicatorContainer{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-transition:color 150ms;transition:color 150ms;color:hsl(0, 0%, 80%);padding:8px;box-sizing:border-box;}.css-1xc3v61-indicatorContainer:hover{color:hsl(0, 0%, 60%);}</style><div class=" css-1xc3v61-indicatorContainer" aria-hidden="true"><style data-emotion="css 8mmkcg">.css-8mmkcg{display:inline-block;fill:currentColor;line-height:1;stroke:currentColor;stroke-width:0;}</style><svg height="20" width="20" viewBox="0 0 20 20" aria-hidden="true" focusable="false" class="css-8mmkcg"><path d="M4.516 7.548c0.436-0.446 1.043-0.481 1.576 0l3.908 3.747 3.908-3.747c0.533-0.481 1.141-0.446 1.574 0 0.436 0.445 0.408 1.197 0 1.615-0.406 0.418-4.695 4.502-4.695 4.502-0.217 0.223-0.502 0.335-0.787 0.335s-0.57-0.112-0.789-0.335c0 0-4.287-4.084-4.695-4.502s-0.436-1.17 0-1.615z"></path></svg></div></div></div></div><div class="CheckRowCount__sectionRow___vyiE6"><label class="CheckRow__checkRow___Wumpa"><input class="fa fa-lg fa-check Checkbox__checkbox___dGd5x " type="checkbox"/><span class="CheckRow__checkRowLabel___ax_ST">Article</span></label><span><span>7</span></span></div></div></div></div><div class="FilterCard__filterCard___bZEVP"><div class="FilterCard__noInput___lsgWM"><div class="FilterCard__filterCardHeader___puB2k" role="button" tabindex="0" aria-label="Expand Relationship"><p class="FilterCard__header___dRl1u Paragraph__body____m5FY Paragraph__bold___PhFOq">Relationship<!-- --> </p></div><div><div class="CheckRowCount__sectionRow___vyiE6"><label class="CheckRow__checkRow___Wumpa"><input class="fa fa-lg fa-check Checkbox__checkbox___dGd5x " type="checkbox"/><span class="CheckRow__checkRowLabel___ax_ST">Self Cite</span></label><span><span>1</span></span></div><div class="CheckRowCount__sectionRow___vyiE6"><label class="CheckRow__checkRow___Wumpa"><input class="fa fa-lg fa-check Checkbox__checkbox___dGd5x " type="checkbox"/><span class="CheckRow__checkRowLabel___ax_ST">Independent</span></label><span><span>6</span></span></div></div></div></div><div class="FilterCard__filterCard___bZEVP"><div class="FilterCard__noInput___lsgWM"><div class="FilterCard__filterCardHeader___puB2k" role="button" tabindex="0" aria-label="Expand Authors"><p class="FilterCard__header___dRl1u Paragraph__body____m5FY Paragraph__bold___PhFOq">Authors<!-- --> </p><div class="OpenerIcon__folder___jiKx6 false undefined"><i class="OpenerIcon__angleDown___QHC0i icon icon-down-carret"></i></div></div></div></div><div class="FilterCard__filterCard___bZEVP"><div class="FilterCard__noInput___lsgWM"><div class="FilterCard__filterCardHeader___puB2k" role="button" tabindex="0" aria-label="Expand Journals"><p class="FilterCard__header___dRl1u Paragraph__body____m5FY Paragraph__bold___PhFOq">Journals<!-- --> </p><div class="OpenerIcon__folder___jiKx6 false undefined"><i class="OpenerIcon__angleDown___QHC0i icon icon-down-carret"></i></div></div></div></div><div class="FiltersSubmit__mobileSpacer___Zot7B"></div><div class="FiltersSubmit__mobileButtons___q8V7A"><button class="FiltersSubmit__button___JlyTu Button__btn___k1xtO Button__btn--transparent___XnBIC Button__size--medium___yX63r">OK</button></div></div></div><div class="ReportPanel__reportButtons___XerGy"><button class="Citations__reportExport___KlHrC Button__btn___k1xtO Button__btn--transparent___XnBIC Button__size--medium___yX63r"><img alt="Export report" src="https://cdn.scite.ai/assets/images/icons/reports/download-csv.svg" width="16px" height="16px"/><span class="Citations__reportExportText___fPVDL">Export report</span></button><div class="ReportPanel__reportButton___fQ0Q4 AddReportToDashboardButton__link___U95EJ"><button class="AddReportToDashboardButton__button___GSCqY Button__btn___k1xtO Button__btn--blue___FBSR2 Button__size--medium___yX63r"><i class="AddReportToDashboardButton__icon___GnVvr fa fa-book-open"></i><span class="AddReportToDashboardButton__text___fO21o">Add to dashboard</span></button></div></div></div><div class="ReportPanel__citationsWrapper___Ik9b3"><div class="Citations__citations___rsiM2"><div class="CitationsHeader__citationsSort___VxgmK"><div class="CitationsHeader__citationsHeader___uQ15D"><div class="CitationsHeader__citeCount___gEx9I CitationsHeader__selected___eJOwX" tabindex="0" role="button"><div class="CitationsHeader__imageTooltip____m9Gf Tooltip__reference___hgPSY"><img class="CitationsHeader__citationsImg___lK2Tq" alt="citations" src="https://cdn.scite.ai/assets/images/icons/citations-icon.svg" height="32px" width="32px"/><h5 class="Header__h5___YDSW4 CitationsHeader__citeHeader___q7Gw4">Cited by <!-- -->19<!-- --> publication<!-- -->s</h5><div class="CitationsHeader__citeHeaderLabel___Zhzp2"> <!-- -->(<!-- -->26<!-- --> citation statement<!-- -->s<!-- -->)</div></div></div><div tabindex="0" role="button" class="CitationsHeader__referencesCount___tubVv"><div class="CitationsHeader__imageTooltip____m9Gf Tooltip__reference___hgPSY"><img class="CitationsHeader__citationsImg___lK2Tq" alt="references" src="https://cdn.scite.ai/assets/images/icons/references-icon.svg" height="32px" width="32px"/><h5 class="Header__h5___YDSW4 CitationsHeader__citeHeader___q7Gw4">References <!-- -->76<!-- --> publication<!-- -->s</h5></div></div></div><div class="CitationsHeader__mobileFilters___xqr8O"><div class="CitationsHeader__mobileClassificationfilter___w6IKl"><div class="Classification__row___s1V6w"><div class="Classification__rowLeft___VoLlX"><label class="CheckRow__checkRow___Wumpa"><input class="fa fa-lg fa-check Checkbox__checkbox___dGd5x " type="checkbox"/><span class="CheckRow__checkRowLabel___ax_ST">Supporting</span></label><div class="Classification__rowType___282g8"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i></div></div><div class="Classification__rowRight___Zxitp"><span class="Classification__count___Y86vw">1</span></div></div><div class="Classification__row___s1V6w"><div class="Classification__rowLeft___VoLlX"><label class="CheckRow__checkRow___Wumpa"><input class="fa fa-lg fa-check Checkbox__checkbox___dGd5x " type="checkbox"/><span class="CheckRow__checkRowLabel___ax_ST">Mentioning</span></label><div class="Classification__rowType___282g8"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i></div></div><div class="Classification__rowRight___Zxitp"><span class="Classification__count___Y86vw">22</span></div></div><div class="Classification__row___s1V6w"><div class="Classification__rowLeft___VoLlX"><label class="CheckRow__checkRow___Wumpa"><input class="fa fa-lg fa-check Checkbox__checkbox___dGd5x " type="checkbox"/><span class="CheckRow__checkRowLabel___ax_ST">Contrasting</span></label><div class="Classification__rowType___282g8"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i></div></div><div class="Classification__rowRight___Zxitp"><span class="Classification__count___Y86vw">0</span></div></div></div><div class="CitationsHeader__searchCitesMobileLayout___Ai7i2"><div class="SearchCites__layout___vB255"><form class="SearchInput__searchInput___ze14_ SearchCites__search___Y_Yhp"><input aria-label="search citations" data-showdropdown="true" autoComplete="off" class="SearchInput__input___D08BX SearchCites__input___dC99x" type="text" placeholder="Context, author(s), title etc." value=""/><div class="SearchInput__button___L2ljx" aria-label="search-button" role="button" tabindex="0"><i class="icon icon-search SearchInput__icon___sEZb9"></i></div></form></div></div><div class="CitationsHeader__sortCitesMobileLayout___FB0xB"><style data-emotion="css b62m3t-container">.css-b62m3t-container{position:relative;box-sizing:border-box;}</style><div class=" css-b62m3t-container"><style data-emotion="css 7pg0cj-a11yText">.css-7pg0cj-a11yText{z-index:9999;border:0;clip:rect(1px, 1px, 1px, 1px);height:1px;width:1px;position:absolute;overflow:hidden;padding:0;white-space:nowrap;}</style><span id="react-select-292784-live-region" class="css-7pg0cj-a11yText"></span><span aria-live="polite" aria-atomic="false" aria-relevant="additions text" class="css-7pg0cj-a11yText"></span><style data-emotion="css 1vom5ua-control">.css-1vom5ua-control{-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;cursor:default;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-box-flex-wrap:wrap;-webkit-flex-wrap:wrap;-ms-flex-wrap:wrap;flex-wrap:wrap;-webkit-box-pack:justify;-webkit-justify-content:space-between;justify-content:space-between;min-height:38px;outline:0!important;position:relative;-webkit-transition:all 100ms;transition:all 100ms;background-color:hsl(0, 0%, 100%);border-color:hsl(0, 0%, 80%);border-radius:12px;border-style:solid;border-width:1px;box-sizing:border-box;}.css-1vom5ua-control:hover{border-color:hsl(0, 0%, 70%);}</style><div class=" css-1vom5ua-control"><style data-emotion="css hlgwow">.css-hlgwow{-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;display:grid;-webkit-flex:1;-ms-flex:1;flex:1;-webkit-box-flex-wrap:wrap;-webkit-flex-wrap:wrap;-ms-flex-wrap:wrap;flex-wrap:wrap;-webkit-overflow-scrolling:touch;position:relative;overflow:hidden;padding:2px 8px;box-sizing:border-box;}</style><div class=" css-hlgwow"><div style="label:singleValue;grid-area:1 / 1 / 2 / 3;max-width:100%;overflow:hidden;text-overflow:ellipsis;white-space:nowrap;color:hsl(0, 0%, 20%);margin-left:2px;margin-right:2px;box-sizing:border-box">Order By: <!-- -->Relevance</div><style data-emotion="css 19bb58m">.css-19bb58m{visibility:visible;-webkit-flex:1 1 auto;-ms-flex:1 1 auto;flex:1 1 auto;display:inline-grid;grid-area:1/1/2/3;grid-template-columns:0 min-content;margin:2px;padding-bottom:2px;padding-top:2px;color:hsl(0, 0%, 20%);box-sizing:border-box;}.css-19bb58m:after{content:attr(data-value) " ";visibility:hidden;white-space:pre;grid-area:1/2;font:inherit;min-width:2px;border:0;margin:0;outline:0;padding:0;}</style><div class=" css-19bb58m" data-value=""><input class="" style="label:input;color:inherit;background:0;opacity:1;width:100%;grid-area:1 / 2;font:inherit;min-width:2px;border:0;margin:0;outline:0;padding:0" autoCapitalize="none" autoComplete="off" autoCorrect="off" id="react-select-292784-input" spellcheck="false" tabindex="0" type="text" aria-autocomplete="list" aria-expanded="false" aria-haspopup="true" role="combobox" value=""/></div></div><style data-emotion="css 1wy0on6">.css-1wy0on6{-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-align-self:stretch;-ms-flex-item-align:stretch;align-self:stretch;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-shrink:0;-ms-flex-negative:0;flex-shrink:0;box-sizing:border-box;}</style><div class=" css-1wy0on6"><span class=" css-0"></span><style data-emotion="css 1xc3v61-indicatorContainer">.css-1xc3v61-indicatorContainer{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-transition:color 150ms;transition:color 150ms;color:hsl(0, 0%, 80%);padding:8px;box-sizing:border-box;}.css-1xc3v61-indicatorContainer:hover{color:hsl(0, 0%, 60%);}</style><div class=" css-1xc3v61-indicatorContainer" aria-hidden="true"><style data-emotion="css 8mmkcg">.css-8mmkcg{display:inline-block;fill:currentColor;line-height:1;stroke:currentColor;stroke-width:0;}</style><svg height="20" width="20" viewBox="0 0 20 20" aria-hidden="true" focusable="false" class="css-8mmkcg"><path d="M4.516 7.548c0.436-0.446 1.043-0.481 1.576 0l3.908 3.747 3.908-3.747c0.533-0.481 1.141-0.446 1.574 0 0.436 0.445 0.408 1.197 0 1.615-0.406 0.418-4.695 4.502-4.695 4.502-0.217 0.223-0.502 0.335-0.787 0.335s-0.57-0.112-0.789-0.335c0 0-4.287-4.084-4.695-4.502s-0.436-1.17 0-1.615z"></path></svg></div></div></div></div></div></div><div class="CitationsHeader__settingsButtonLayout___SCS1l"><button class="SettingsButton__btn___P6KmW Button__btn___k1xtO Button__btn--transparent___XnBIC Button__size--medium___yX63r Button__tiny___hya9X" aria-label="Settings button"><i class="SettingsButton__icon___w15lK fa fa-sliders-h"></i><span>Settings</span></button></div></div><div class="PapersList__citationList___nW0RR"><div style="opacity:1;pointer-events:auto"><div class="PaperCard__paperCard___Tkx_L PaperCard__card___rYfBl"><div><div><div class="Citation__citation___I7BGj Citation__citationGrid___yNzom"><div class="Citation__rightCol___rqdSW"><div class="Citation__snippetLayout___VCTXv"><div class="Snippet__snippetWrapper___pL8c1"><span><span><div>“…On one hand, their activity as gatekeepers of adaptive immunity is needed <cite data-doi="10.1158/1078-0432.ccr-18-0047">[41]</cite>, but on the other hand, an inflammatory T-cell phenotype boosts tumor progression. In GBM, the proinflammatory cytokines IL-17 and IL-22 have been identified as cancer-promoting molecules activating oncogenic STAT3 signaling, thereby protecting GBM cells from apoptosis, promoting GBM proliferation and enhancing invasion <cite data-doi="10.1371/journal.pone.0119872">[26,</cite><cite class="target" data-doi="10.4172/2325-9701.s1-004">27,</cite><cite data-doi="10.1111/jcmm.13938">44]</cite>. IL-22 plays a particularly important role in immune cell-tumor interactions, as it is solely secreted by immune cells and exerts its effects only on non-hematopoietic cells <cite data-doi="10.1002/eji.201747183">[45]</cite>.…”</div></span></span></div></div><div class="Citation__citeInfo___v24kU"><span class="Citation__section___YjAW3"><b>Section</b>: <!-- -->Discussion</span><span class="Citation__typeInfo___s7iNF"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="Citation__citationType___LuRbr">mentioning</span><div class="Tooltip__reference___hgPSY"><div class="Citation__classificationDetails___xRtK5"><span class="Citation__classificationDetail___vPtBx">confidence: <!-- -->99%</span></div></div></span></div></div><div class="Citation__actions___STMoF"><div class="Tooltip__reference___hgPSY"><i class="CopyButton__copyButton___I1ybw fa fa-copy" role="button" tabindex="0"></i></div><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div><div aria-hidden="true" class="PaperCard__expandingWrapper___JmHu_" style="overflow:hidden;height:0;opacity:0"><div style="width:fit-content"><div class="Citation__citation___I7BGj Citation__citationGrid___yNzom"><div class="Citation__rightCol___rqdSW"><div class="Citation__snippetLayout___VCTXv"><div class="Snippet__snippetWrapper___pL8c1"><span><span><div>“…We assumed that anakinra might also affect these aspects of tumor-associated inflammation. We thus extracted T cells after indirect co-culture of PBMCs and GBM cells and analyzed expression levels of inflammatory cytokines that were (a) secreted by T cells and (b) involved in oncogenic signaling <cite data-doi="10.1073/pnas.1705165114">[25]</cite><cite data-doi="10.1371/journal.pone.0119872">[26]</cite><cite class="target" data-doi="10.4172/2325-9701.s1-004">[27]</cite>. After administration of anakinra, we detected a marked decrease of proinflammatory IFNγ, IL-17, and IL-22 mRNA expression ( Figure 5A: IFNγ: −85.0% ± 45.4%, IL-17: −88.1% ± 21.7%, IL-22: −63.2% ± 22.0%, n = 13, p < 0.004) in these T cells as well as reduced protein levels in the respective conditioned medium ( Figure 5A: IFNγ: −13.04% ±3.3, IL-17: −51.8% ± 20.8%, IL-22: −37.1% ± 8.5%, n = 10, p < 0.004).…”</div></span></span></div></div><div class="Citation__citeInfo___v24kU"><span class="Citation__section___YjAW3"><b>Section</b>: <!-- -->Anakinra Reduced Inflammatory Signaling In Lymphocytes Co-cu</span><span class="Citation__typeInfo___s7iNF"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="Citation__citationType___LuRbr">mentioning</span><div class="Tooltip__reference___hgPSY"><div class="Citation__classificationDetails___xRtK5"><span class="Citation__classificationDetail___vPtBx">confidence: <!-- -->99%</span></div></div></span></div></div><div class="Citation__actions___STMoF"><div class="Tooltip__reference___hgPSY"><i class="CopyButton__copyButton___I1ybw fa fa-copy" role="button" tabindex="0"></i></div><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div></div></div><span class="PaperCard__expandCard___m8Yf4" role="button" tabindex="0"><div class="OpenerIcon__folder___jiKx6 false undefined"><i class="OpenerIcon__angleDown___QHC0i icon icon-down-carret"></i></div>See 1 more Smart Citation</span><div class="PaperCard__grid___NMQAD"><div class="PaperCard__abstractWrapper___Yq394"><div class="Paper__paper___CWi0y"><a class="Paper__title___WkJQP Link__link___plGt2 Link__bold___JGJNO Paper__title___WkJQP" tabindex="0" href="/reports/the-il-1-antagonist-anakinra-attenuates-mOLnMEre"><h3 class="Paper__title___WkJQP">The IL-1 Antagonist Anakinra Attenuates Glioblastoma Aggressiveness by Dampening Tumor-Associated Inflammation</h3></a><div class="Paper__referenceLine___quVTP"><div class="Authors__authors___uWMEz Paper__lineItem___FXrg7"><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/max-hubner-4LjZO3"><span>Hübner</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/lmu-klinikum-bNQp">1</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/david-effinger-WxN6ed"><span>Effinger</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/lmu-klinikum-bNQp">2</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/tingting-wang-D1z1RP"><span>Wang</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/lmu-klinikum-bNQp">3</a></sup></div><span> </span></div><span class="Authors__link___k07oy">et al.</span><span> <!-- -->2020</span></div><span class="Paper__lineItem___FXrg7"><span class="Reference__reference___AIzFu"><span><a class="Link__link___plGt2 Link__underline___K1Y7j" tabindex="0" href="/journals/cancers-dvlO3"><em>Cancers</em></a></span></span></span></div><div class="Paper__tallyLayout___k19c4"><a class="HorizontalTally__horizontalTally___gMrpx" href="/reports/the-il-1-antagonist-anakinra-attenuates-mOLnMEre"><div class="HorizontalTally__inner___AzKR8"><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--publications___MBaqU icon-publications"></i><span class="HorizontalTally__count___ZuxQA">16</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="HorizontalTally__count___ZuxQA">12</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div></div></a></div><div class="Paper__linksLayout___Ql9Qd"><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" href="https://doi.org/10.3390/cancers12020433" tabindex="0" role="link" target="_blank" rel="noopener noreferrer nofollow">View full text</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Add to dashboard</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Cite</a></div></div><div aria-hidden="true" style="overflow:hidden;height:0;opacity:0"><div style="width:auto"><p class="Abstract__abstract___V8wNr PaperCard__abstract___lR5RS Paragraph__body____m5FY"><span><span>Background: The recombinant IL-1 receptor antagonist anakinra—currently approved for the treatment of autoinflammatory diseases—blocks IL-1β-mediated inflammatory signaling. As inflammation is a major driver of cancer, we hypothesized that anakinra might be able to mitigate glioblastoma (GBM) aggressiveness. Methods: Primary GBM or T98G cells were incubated alone or with peripheral blood mononuclear cells (PBMCs) and were subsequently treated with IL-1β and/or anakinra. T cells were obtained by magnetic bead isolation. Protein and mRNA expression were quantified by SDS-PAGE, qRT-PCR, and ELISA, respectively. Cell proliferation and apoptosis were analyzed via flow cytometry. Chemotaxis was studied via time-lapse microscopy. Results: Upon IL-1β stimulation, anakinra attenuated proinflammatory gene expression in both GBM cells and PBMCs, and mitigated tumor migration and proliferation. In a more lifelike model replacing IL-1β stimulation by GBM–PBMC co-culture, sole presence of PBMCs proved sufficient to induce a proinflammatory phenotype in GBM cells with enhanced proliferation and migration rates and attenuated apoptosis. Anakinra antagonized these pro-tumorigenic effects and, moreover, reduced inflammatory signaling in T cells without compromising anti-tumor effector molecules. Conclusion: By dampening the inflammatory crosstalk between GBM and immune cells, anakinra mitigated GBM aggressiveness. Hence, counteracting IL-1β-mediated inflammation might be a promising strategy to pursue.</span></span></p></div></div></div><div class="PaperCard__menu___wXkM0"><a class="PaperCard__textButton___ncs_Z" tabindex="0">show abstract</a><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div><div class="PapersList__paywalledCites___XIuJQ"><div class="PapersList__paperCardsLayout___dtzN9"><div class="PaperCard__paperCard___Tkx_L PaperCard__card___rYfBl"><div><div><div class="Citation__citation___I7BGj Citation__citationGrid___yNzom"><div class="Citation__rightCol___rqdSW"><div class="Citation__snippetLayout___VCTXv"><div class="Snippet__snippetWrapper___pL8c1"><span><span><div>“…On one hand, their activity as gatekeepers of adaptive immunity is needed <cite data-doi="10.1158/1078-0432.ccr-18-0047">[41]</cite>, but on the other hand, an inflammatory T-cell phenotype boosts tumor progression. In GBM, the proinflammatory cytokines IL-17 and IL-22 have been identified as cancer-promoting molecules activating oncogenic STAT3 signaling, thereby protecting GBM cells from apoptosis, promoting GBM proliferation and enhancing invasion <cite data-doi="10.1371/journal.pone.0119872">[26,</cite><cite class="target" data-doi="10.4172/2325-9701.s1-004">27,</cite><cite data-doi="10.1111/jcmm.13938">44]</cite>. IL-22 plays a particularly important role in immune cell-tumor interactions, as it is solely secreted by immune cells and exerts its effects only on non-hematopoietic cells <cite data-doi="10.1002/eji.201747183">[45]</cite>.…”</div></span></span></div></div><div class="Citation__citeInfo___v24kU"><span class="Citation__section___YjAW3"><b>Section</b>: <!-- -->Discussion</span><span class="Citation__typeInfo___s7iNF"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="Citation__citationType___LuRbr">mentioning</span><div class="Tooltip__reference___hgPSY"><div class="Citation__classificationDetails___xRtK5"><span class="Citation__classificationDetail___vPtBx">confidence: <!-- -->99%</span></div></div></span></div></div><div class="Citation__actions___STMoF"><div class="Tooltip__reference___hgPSY"><i class="CopyButton__copyButton___I1ybw fa fa-copy" role="button" tabindex="0"></i></div><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div><div class="Citation__citation___I7BGj Citation__citationGrid___yNzom"><div class="Citation__rightCol___rqdSW"><div class="Citation__snippetLayout___VCTXv"><div class="Snippet__snippetWrapper___pL8c1"><span><span><div>“…We assumed that anakinra might also affect these aspects of tumor-associated inflammation. We thus extracted T cells after indirect co-culture of PBMCs and GBM cells and analyzed expression levels of inflammatory cytokines that were (a) secreted by T cells and (b) involved in oncogenic signaling <cite data-doi="10.1073/pnas.1705165114">[25]</cite><cite data-doi="10.1371/journal.pone.0119872">[26]</cite><cite class="target" data-doi="10.4172/2325-9701.s1-004">[27]</cite>. After administration of anakinra, we detected a marked decrease of proinflammatory IFNγ, IL-17, and IL-22 mRNA expression ( Figure 5A: IFNγ: −85.0% ± 45.4%, IL-17: −88.1% ± 21.7%, IL-22: −63.2% ± 22.0%, n = 13, p < 0.004) in these T cells as well as reduced protein levels in the respective conditioned medium ( Figure 5A: IFNγ: −13.04% ±3.3, IL-17: −51.8% ± 20.8%, IL-22: −37.1% ± 8.5%, n = 10, p < 0.004).…”</div></span></span></div></div><div class="Citation__citeInfo___v24kU"><span class="Citation__section___YjAW3"><b>Section</b>: <!-- -->Anakinra Reduced Inflammatory Signaling In Lymphocytes Co-cu</span><span class="Citation__typeInfo___s7iNF"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="Citation__citationType___LuRbr">mentioning</span><div class="Tooltip__reference___hgPSY"><div class="Citation__classificationDetails___xRtK5"><span class="Citation__classificationDetail___vPtBx">confidence: <!-- -->99%</span></div></div></span></div></div><div class="Citation__actions___STMoF"><div class="Tooltip__reference___hgPSY"><i class="CopyButton__copyButton___I1ybw fa fa-copy" role="button" tabindex="0"></i></div><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div><div aria-hidden="true" class="PaperCard__expandingWrapper___JmHu_" style="overflow:hidden;height:0;opacity:0"><div style="width:fit-content"></div></div></div><div class="PaperCard__grid___NMQAD"><div class="PaperCard__abstractWrapper___Yq394"><div class="Paper__paper___CWi0y"><a class="Paper__title___WkJQP Link__link___plGt2 Link__bold___JGJNO Paper__title___WkJQP" tabindex="0" href="/reports/the-il-1-antagonist-anakinra-attenuates-mOLnMEre"><h3 class="Paper__title___WkJQP">The IL-1 Antagonist Anakinra Attenuates Glioblastoma Aggressiveness by Dampening Tumor-Associated Inflammation</h3></a><div class="Paper__referenceLine___quVTP"><div class="Authors__authors___uWMEz Paper__lineItem___FXrg7"><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/max-hubner-4LjZO3"><span>Hübner</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/lmu-klinikum-bNQp">1</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/david-effinger-WxN6ed"><span>Effinger</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/lmu-klinikum-bNQp">2</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/tingting-wang-D1z1RP"><span>Wang</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/lmu-klinikum-bNQp">3</a></sup></div><span> </span></div><span class="Authors__link___k07oy">et al.</span><span> <!-- -->2020</span></div><span class="Paper__lineItem___FXrg7"><span class="Reference__reference___AIzFu"><span><a class="Link__link___plGt2 Link__underline___K1Y7j" tabindex="0" href="/journals/cancers-dvlO3"><em>Cancers</em></a></span></span></span></div><div class="Paper__tallyLayout___k19c4"><a class="HorizontalTally__horizontalTally___gMrpx" href="/reports/the-il-1-antagonist-anakinra-attenuates-mOLnMEre"><div class="HorizontalTally__inner___AzKR8"><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--publications___MBaqU icon-publications"></i><span class="HorizontalTally__count___ZuxQA">16</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="HorizontalTally__count___ZuxQA">12</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div></div></a></div><div class="Paper__linksLayout___Ql9Qd"><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" href="https://doi.org/10.3390/cancers12020433" tabindex="0" role="link" target="_blank" rel="noopener noreferrer nofollow">View full text</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Add to dashboard</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Cite</a></div></div><div aria-hidden="true" style="overflow:hidden;height:0;opacity:0"><div style="width:auto"><p class="Abstract__abstract___V8wNr PaperCard__abstract___lR5RS Paragraph__body____m5FY"><span><span>Background: The recombinant IL-1 receptor antagonist anakinra—currently approved for the treatment of autoinflammatory diseases—blocks IL-1β-mediated inflammatory signaling. As inflammation is a major driver of cancer, we hypothesized that anakinra might be able to mitigate glioblastoma (GBM) aggressiveness. Methods: Primary GBM or T98G cells were incubated alone or with peripheral blood mononuclear cells (PBMCs) and were subsequently treated with IL-1β and/or anakinra. T cells were obtained by magnetic bead isolation. Protein and mRNA expression were quantified by SDS-PAGE, qRT-PCR, and ELISA, respectively. Cell proliferation and apoptosis were analyzed via flow cytometry. Chemotaxis was studied via time-lapse microscopy. Results: Upon IL-1β stimulation, anakinra attenuated proinflammatory gene expression in both GBM cells and PBMCs, and mitigated tumor migration and proliferation. In a more lifelike model replacing IL-1β stimulation by GBM–PBMC co-culture, sole presence of PBMCs proved sufficient to induce a proinflammatory phenotype in GBM cells with enhanced proliferation and migration rates and attenuated apoptosis. Anakinra antagonized these pro-tumorigenic effects and, moreover, reduced inflammatory signaling in T cells without compromising anti-tumor effector molecules. Conclusion: By dampening the inflammatory crosstalk between GBM and immune cells, anakinra mitigated GBM aggressiveness. Hence, counteracting IL-1β-mediated inflammation might be a promising strategy to pursue.</span></span></p></div></div></div><div class="PaperCard__menu___wXkM0"><a class="PaperCard__textButton___ncs_Z" tabindex="0">show abstract</a><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div><div class="PaperCard__paperCard___Tkx_L PaperCard__card___rYfBl"><div><div><div class="Citation__citation___I7BGj Citation__citationGrid___yNzom"><div class="Citation__rightCol___rqdSW"><div class="Citation__snippetLayout___VCTXv"><div class="Snippet__snippetWrapper___pL8c1"><span><span><div>“…The cytokine profile as well as the type and density of immune cells in the tumor microenvironment have been shown to play a critical role in the progression of malignant tumors [ <cite data-doi="10.2217/14796694.4.3.433"> 38 </cite> – <cite data-doi="10.1126/science.1129139"> 40 </cite> ]. Our group and others have demonstrated the infiltration/enhancement of IL-17-producing cells in malignant gliomas [ <cite data-doi="10.1007/s00262-012-1312-7"> 32 </cite> – <cite data-doi="10.1016/j.intimp.2011.03.015"> 34 </cite> , <cite data-doi="10.1371/journal.pone.0015390"> 36 </cite> ] and IL-17 has been linked to cancer progression in many tumor types [ <cite class="target" data-doi="10.4172/2325-9701.s1-004"> 33 </cite> , <cite data-doi="10.1002/ijc.24497"> 41 </cite> – <cite data-doi="10.1177/147323001003800223"> 44 </cite> ]. IL-17 over-expression potentially enhance glioma cell growth in vivo , which may be associated with accelerated angiogenesis [ <cite data-doi="10.3892/ol.2013.1518"> 45 </cite> ].…”</div></span></span></div></div><div class="Citation__citeInfo___v24kU"><span class="Citation__section___YjAW3"><b>Section</b>: <!-- -->Discussion</span><span class="Citation__typeInfo___s7iNF"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="Citation__citationType___LuRbr">mentioning</span><div class="Tooltip__reference___hgPSY"><div class="Citation__classificationDetails___xRtK5"><span class="Citation__classificationDetail___vPtBx">confidence: <!-- -->99%</span></div></div></span></div></div><div class="Citation__actions___STMoF"><div class="Tooltip__reference___hgPSY"><i class="CopyButton__copyButton___I1ybw fa fa-copy" role="button" tabindex="0"></i></div><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div><div class="Citation__citation___I7BGj Citation__citationGrid___yNzom"><div class="Citation__rightCol___rqdSW"><div class="Citation__snippetLayout___VCTXv"><div class="Snippet__snippetWrapper___pL8c1"><span><span><div>“…More importantly, both these studies did not analyze the status of IL-17R expression in the tumor cells. Overall, the role of IL-17 in glioma progression remains uncertain and the precise underlying mechanisms remain largely unknown [ <cite class="target" data-doi="10.4172/2325-9701.s1-004"> 33 </cite> ]. In the current study, we have demonstrated a potential impact of IL-17-IL-17R interaction in glioma growth and progression via direct stimulation of the GSCs.…”</div></span></span></div></div><div class="Citation__citeInfo___v24kU"><span class="Citation__section___YjAW3"><b>Section</b>: <!-- -->Discussion</span><span class="Citation__typeInfo___s7iNF"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="Citation__citationType___LuRbr">mentioning</span><div class="Tooltip__reference___hgPSY"><div class="Citation__classificationDetails___xRtK5"><span class="Citation__classificationDetail___vPtBx">confidence: <!-- -->99%</span></div></div></span></div></div><div class="Citation__actions___STMoF"><div class="Tooltip__reference___hgPSY"><i class="CopyButton__copyButton___I1ybw fa fa-copy" role="button" tabindex="0"></i></div><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div><div aria-hidden="true" class="PaperCard__expandingWrapper___JmHu_" style="overflow:hidden;height:0;opacity:0"><div style="width:fit-content"><div class="Citation__citation___I7BGj Citation__citationGrid___yNzom"><div class="Citation__rightCol___rqdSW"><div class="Citation__snippetLayout___VCTXv"><div class="Snippet__snippetWrapper___pL8c1"><span><span><div>“…GSCs were first identified and purified from human brain tumors by Singh et al as a population of CD133 + tumor cells [ 49 , <cite data-doi="10.1038/nature03128"> 50 </cite> ]. While several studies have reaffirmed strong association of CD133 with GSCs, the intermediate filament protein Nestin and the transcription factor Sox2 have also often been reported in GSCs [ <cite data-doi="10.1016/j.cell.2014.02.030"> 8 </cite> , <cite class="target" data-doi="10.4172/2325-9701.s1-004"> 33 </cite> , <cite data-doi="10.3748/wjg.v17.i4.409"> 51 </cite> – <cite data-doi="10.1002/ijc.24402"> 54 </cite> ]. Sox2 plays a critical role in the induction or maintenance of glioma ‘stemness’ [ <cite data-doi="10.1016/j.cell.2014.02.030"> 8 </cite> , <cite data-doi="10.1074/jbc.m111.300863"> 55 </cite> ].…”</div></span></span></div></div><div class="Citation__citeInfo___v24kU"><span class="Citation__section___YjAW3"><b>Section</b>: <!-- -->Discussion</span><span class="Citation__typeInfo___s7iNF"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="Citation__citationType___LuRbr">mentioning</span><div class="Tooltip__reference___hgPSY"><div class="Citation__classificationDetails___xRtK5"><span class="Citation__classificationDetail___vPtBx">confidence: <!-- -->99%</span></div></div></span></div></div><div class="Citation__actions___STMoF"><div class="Tooltip__reference___hgPSY"><i class="CopyButton__copyButton___I1ybw fa fa-copy" role="button" tabindex="0"></i></div><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div></div></div><span class="PaperCard__expandCard___m8Yf4" role="button" tabindex="0"><div class="OpenerIcon__folder___jiKx6 false undefined"><i class="OpenerIcon__angleDown___QHC0i icon icon-down-carret"></i></div>See 1 more Smart Citation</span><div class="PaperCard__grid___NMQAD"><div class="PaperCard__abstractWrapper___Yq394"><div class="Paper__paper___CWi0y"><a class="Paper__title___WkJQP Link__link___plGt2 Link__bold___JGJNO Paper__title___WkJQP" tabindex="0" href="/reports/preferential-expression-of-functional-il-17r-9QwNpE"><h3 class="Paper__title___WkJQP">Preferential expression of functional IL-17R in glioma stem cells: potential role in self-renewal</h3></a><div class="Paper__referenceLine___quVTP"><div class="Authors__authors___uWMEz Paper__lineItem___FXrg7"><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/prahlad-parajuli-5Gl4gV"><span>Parajuli</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/karmanos-cancer-institute-G5z6L">1</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/rohit-anand-PQkgaR"><span>Anand</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/karmanos-cancer-institute-G5z6L">2</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/chandramouli-mandalaparty-aMOOK"><span>Mandalaparty</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/karmanos-cancer-institute-G5z6L">3</a></sup></div><span> </span></div><span class="Authors__link___k07oy">et al.</span><span> <!-- -->2016</span></div><span class="Paper__lineItem___FXrg7"><span class="Reference__reference___AIzFu"><span><a class="Link__link___plGt2 Link__underline___K1Y7j" tabindex="0" href="/journals/oncotarget-lZQVv"><em>Oncotarget</em></a></span><span class="Badge__pill___QnwOm Reference__preprintBadge___m9cqn"><span><div class="Tooltip__reference___hgPSY">Self Cite</div></span></span></span></span></div><div class="Paper__tallyLayout___k19c4"><a class="HorizontalTally__horizontalTally___gMrpx" href="/reports/preferential-expression-of-functional-il-17r-9QwNpE"><div class="HorizontalTally__inner___AzKR8"><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--publications___MBaqU icon-publications"></i><span class="HorizontalTally__count___ZuxQA">34</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="HorizontalTally__count___ZuxQA">24</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div></div></a></div><div class="Paper__linksLayout___Ql9Qd"><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" href="https://doi.org/10.18632/oncotarget.6847" tabindex="0" role="link" target="_blank" rel="noopener noreferrer nofollow">View full text</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Add to dashboard</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Cite</a></div></div><div aria-hidden="true" style="overflow:hidden;height:0;opacity:0"><div style="width:auto"><p class="Abstract__abstract___V8wNr PaperCard__abstract___lR5RS Paragraph__body____m5FY"><span><span>Gliomas are the most common primary brain tumor and one of the most lethal solid tumors. Mechanistic studies into identification of novel biomarkers are needed to develop new therapeutic strategies for this deadly disease. The objective for this study was to explore the potential direct impact of IL-17−IL-17R interaction in gliomas. Immunohistochemistry and flow cytometry analysis of 12 tumor samples obtained from patients with high grade gliomas revealed that a considerable population (2–19%) of cells in all malignant gliomas expressed IL-17RA, with remarkable co-expression of the glioma stem cell (GSC) markers CD133, Nestin, and Sox2. IL-17 enhanced the self-renewal of GSCs as determined by proliferation and Matrigel® colony assays. IL-17 also induced cytokine/chemokine (IL-6, IL-8, interferon-γ-inducible protein [IP-10], and monocyte chemoattractant protein-1 [MCP-1]) secretion in GSCs, which were differentially blocked by antibodies against IL-17R and IL-6R. Western blot analysis showed that IL-17 modulated the activity of signal transducer and activator of transcription 3 (STAT3), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), glycogen synthase kinase-3β (GSK-3β) and β-catenin in GSCs. While IL-17R-mediated secretion of IL-6 and IL-8 were significantly blocked by inhibitors of NF-κB and STAT3; NF-κB inhibitor was more potent than STAT3 inhibitor in blocking IL-17-induced MCP-1 secretion. Overall, our results suggest that IL-17–IL-17R interaction in GSCs induces an autocrine/paracrine cytokine feedback loop, which may provide an important signaling component for maintenance/self-renewal of GSCs via constitutive activation of both NF-κB and STAT3. The results also strongly implicate IL-17R as an important functional biomarker for therapeutic targeting of GSCs.</span></span></p></div></div></div><div class="PaperCard__menu___wXkM0"><a class="PaperCard__textButton___ncs_Z" tabindex="0">show abstract</a><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div><div class="PaperCard__paperCard___Tkx_L PaperCard__card___rYfBl"><div><div></div><div aria-hidden="true" class="PaperCard__expandingWrapper___JmHu_" style="overflow:hidden;height:0;opacity:0"><div style="width:fit-content"></div></div></div><div class="PaperCard__grid___NMQAD"><div class="PaperCard__abstractWrapper___Yq394"><div class="Paper__paper___CWi0y"><a class="Paper__title___WkJQP Link__link___plGt2 Link__bold___JGJNO Paper__title___WkJQP" tabindex="0" href="/reports/dc-vaccines-loaded-with-glioma-ZG61RgPg"><h3 class="Paper__title___WkJQP">DC vaccines loaded with glioma cells killed by photodynamic therapy induce Th17 anti-tumor immunity and provide a four-gene signature for glioma prognosis</h3></a><div class="Paper__referenceLine___quVTP"><div class="Authors__authors___uWMEz Paper__lineItem___FXrg7"><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/maria-vedunova-EWz6k1"><span>Vedunova</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/n-i-lobachevsky-state-university-6Dk1">1</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/victoria-d-turubanova-ay18dp"><span>Turubanova</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/n-i-lobachevsky-state-university-6Dk1">2</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/o-s-vershinina-wZYJ6a"><span>Vershinina</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/n-i-lobachevsky-state-university-6Dk1">3</a></sup></div><span> </span></div><span class="Authors__link___k07oy">et al.</span><span> <!-- -->2022</span></div><span class="Paper__lineItem___FXrg7"><span class="Reference__reference___AIzFu"><span><a class="Link__link___plGt2 Link__underline___K1Y7j" tabindex="0" href="/journals/cell-death-and-disease-zRQY3"><em>Cell Death Dis</em></a></span></span></span></div><div class="Paper__tallyLayout___k19c4"><a class="HorizontalTally__horizontalTally___gMrpx" href="/reports/dc-vaccines-loaded-with-glioma-ZG61RgPg"><div class="HorizontalTally__inner___AzKR8"><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--publications___MBaqU icon-publications"></i><span class="HorizontalTally__count___ZuxQA">23</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="HorizontalTally__count___ZuxQA">8</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div></div></a></div><div class="Paper__linksLayout___Ql9Qd"><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" href="https://doi.org/10.1038/s41419-022-05514-0" tabindex="0" role="link" target="_blank" rel="noopener noreferrer nofollow">View full text</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Add to dashboard</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Cite</a></div></div><div aria-hidden="true" style="overflow:hidden;height:0;opacity:0"><div style="width:auto"><p class="Abstract__abstract___V8wNr PaperCard__abstract___lR5RS Paragraph__body____m5FY"><span><span>Gliomas, the most frequent type of primary tumor of the central nervous system in adults, results in significant morbidity and mortality. Despite the development of novel, complex, multidisciplinary, and targeted therapies, glioma therapy has not progressed much over the last decades. Therefore, there is an urgent need to develop novel patient-adjusted immunotherapies that actively stimulate antitumor T cells, generate long-term memory, and result in significant clinical benefits. This work aimed to investigate the efficacy and molecular mechanism of dendritic cell (DC) vaccines loaded with glioma cells undergoing immunogenic cell death (ICD) induced by photosens-based photodynamic therapy (PS-PDT) and to identify reliable prognostic gene signatures for predicting the overall survival of patients. Analysis of the transcriptional program of the ICD-based DC vaccine led to the identification of robust induction of Th17 signature when used as a vaccine. These DCs demonstrate retinoic acid receptor-related orphan receptor-γt dependent efficacy in an orthotopic mouse model. Moreover, comparative analysis of the transcriptome program of the ICD-based DC vaccine with transcriptome data from the TCGA-LGG dataset identified a four-gene signature (CFH, GALNT3, SMC4, VAV3) associated with overall survival of glioma patients. This model was validated on overall survival of CGGA-LGG, TCGA-GBM, and CGGA-GBM datasets to determine whether it has a similar prognostic value. To that end, the sensitivity and specificity of the prognostic model for predicting overall survival were evaluated by calculating the area under the curve of the time-dependent receiver operating characteristic curve. The values of area under the curve for TCGA-LGG, CGGA-LGG, TCGA-GBM, and CGGA-GBM for predicting five-year survival rates were, respectively, 0.75, 0.73, 0.9, and 0.69. These data open attractive prospects for improving glioma therapy by employing ICD and PS-PDT-based DC vaccines to induce Th17 immunity and to use this prognostic model to predict the overall survival of glioma patients.</span></span></p></div></div></div><div class="PaperCard__menu___wXkM0"><a class="PaperCard__textButton___ncs_Z" tabindex="0">show abstract</a><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div></div></div></div><div class="PapersList__loading___Yxc5F" style="opacity:0;pointer-events:none"><div data-testid="circle-spinner" class="CircleSpinner__sciteLoadingRing___nlTrH" style="width:80px;height:80px"><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div></div></div></div></div></div></div></div></div></div></div><div class="Footer__layout___jrAhC"><div class="Footer__mainLayout___MVOfi"><div class="Footer__aboutContainer___TwE0S"><img width="128px" height="41px" alt="scite logo" src="https://cdn.scite.ai/assets/images/logo.svg"/><p class="Paragraph__body____m5FY">scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.</p><div class="Footer__contact___DGc_M"><h6 class="Header__h6___QzBvp">Contact Info</h6><div><p class="Footer__address___VMUTY Paragraph__body____m5FY">customersupport@researchsolutions.com</p><p class="Footer__address___VMUTY Paragraph__body____m5FY">10624 S. Eastern Ave., Ste. A-614</p><p class="Footer__address___VMUTY Paragraph__body____m5FY">Henderson, NV 89052, USA</p></div></div></div><div class="Footer__productContainer___wG2mf"><div><h6 class="Header__h6___QzBvp">Product</h6><div class="Footer__products___wIN0z"><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/extension-install">Browser Extension</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/assistant">Assistant by scite</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/search/citations">Citation Statement Search</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/?referenceCheck=true">Reference Check</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/visualizations/global-analysis-of-genome-transcriptome-9L4dJr?dois[0]=10.1038%2Fmsb.2012.40&dois[1]=10.7554%2Felife.05068&focusedElement=10.7554%2Felife.05068">Visualizations</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/create-dashboard">Dashboards</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/journals">Explore Journals</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/affiliations">Explore Organizations</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/institutions">Explore Funders</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/badge">Embedding Badge</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/embed-citation-search">Embedding Citation Search</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/pricing">Pricing</a></div></div><div><h6 class="Header__h6___QzBvp">Resources</h6><div class="Footer__resources___N8pen"><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" href="https://scite.ai/blog" tabindex="0" role="link" target="_blank" rel="noopener noreferrer">Blog</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" href="https://help.researchsolutions.com/hc/en-us/categories/31947397460116-Scite" tabindex="0" role="link" target="_blank" rel="noopener noreferrer">Help & FAQ</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/accessibility-statement">Accessibility Statement</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/apiterms">API Terms</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/partners/academic-institutions">For Universities & Governments</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/partners/researchers">For Researchers</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/partners/publishers">For Publishers</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/partners/pharmaceuticals-and-biotech">For Corporate, Pharma & Enterprise</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/author-marketing">Author Marketing</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" target="_blank" rel="noopener noreferrer" href="/affiliate">Become an Affiliate</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/pricing?tab=organizations">Get an organization trial or quote</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/data-and-services">scite Data & Services</a></div></div><div><h6 class="Header__h6___QzBvp">About</h6><div class="Footer__about___guUpd"><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" target="_blank" rel="noopener noreferrer" href="/news-and-press">News & Press</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/jobs">Careers</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" href="https://direct.mit.edu/qss/article/2/3/882/102990/scite-A-smart-citation-index-that-displays-the" tabindex="0" role="link">Read our Paper</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/data-and-services">Coverage</a></div></div></div></div><div class="Footer__recaptchaInfo___uzydh"><p class="Paragraph__body____m5FY">This site is protected by reCAPTCHA and the Google<!-- --> <a class="Link__link___plGt2 Link__underline___K1Y7j" href="https://policies.google.com/privacy" tabindex="0" role="link" target="_blank" rel="noopener noreferrer">Privacy Policy</a> <!-- -->and<!-- --> <a class="Link__link___plGt2 Link__underline___K1Y7j" href="https://policies.google.com/terms" tabindex="0" role="link" target="_blank" rel="noopener noreferrer">Terms of Service</a> <!-- -->apply.</p></div><div class="Footer__staticContainer___STnbm"><div class="Footer__staticLayout___KI3Dv"><p class="Footer__staticLinks___luYcW Paragraph__small___OZxzF"><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" href="https://scite.ai/blog" tabindex="0" role="link" target="_blank" rel="noopener noreferrer">Blog</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/terms">Terms and Conditions</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/apiterms">API Terms</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" href="/policy">Privacy Policy</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" href="mailto:customersupport@researchsolutions.com" tabindex="0" role="link">Contact</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" role="button">Cookie Preferences</a><a class="Footer__link____xReJ Link__link___plGt2 Footer__link____xReJ" tabindex="0" role="button">Do Not Sell or Share My Personal Information</a></p><div class="Footer__iconsLayout___av51Y"><a class="SocialIcon__socialIcon___gm1fE Footer__icon___m4hTr Link__link___plGt2 SocialIcon__socialIcon___gm1fE Footer__icon___m4hTr" href="https://twitter.com/scite" tabindex="0" role="link" target="_blank" rel="noopener noreferrer" aria-label="https://twitter.com/scite"><i class="icon icon-twitter-new"></i></a><a class="SocialIcon__socialIcon___gm1fE Footer__icon___m4hTr Link__link___plGt2 SocialIcon__socialIcon___gm1fE Footer__icon___m4hTr" href="https://facebook.com/sciteai" tabindex="0" role="link" target="_blank" rel="noopener noreferrer" aria-label="https://facebook.com/sciteai"><i class="icon icon-facebook-new"></i></a><a class="SocialIcon__socialIcon___gm1fE Footer__icon___m4hTr Link__link___plGt2 SocialIcon__socialIcon___gm1fE Footer__icon___m4hTr" href="https://www.instagram.com/scite.ai/" tabindex="0" role="link" target="_blank" rel="noopener noreferrer" aria-label="https://www.instagram.com/scite.ai/"><i class="icon icon-instagram-new"></i></a><a class="SocialIcon__socialIcon___gm1fE Footer__icon___m4hTr Link__link___plGt2 SocialIcon__socialIcon___gm1fE Footer__icon___m4hTr" href="https://www.tiktok.com/@scite.ai" tabindex="0" role="link" target="_blank" rel="noopener noreferrer" aria-label="https://www.tiktok.com/@scite.ai"><i class="icon icon-tiktok"></i></a><a class="SocialIcon__socialIcon___gm1fE Footer__icon___m4hTr Link__link___plGt2 SocialIcon__socialIcon___gm1fE Footer__icon___m4hTr" href="https://www.linkedin.com/company/sciteai/" tabindex="0" role="link" target="_blank" rel="noopener noreferrer" aria-label="https://www.linkedin.com/company/sciteai/"><i class="icon icon-linkedin-new"></i></a><a class="SocialIcon__socialIcon___gm1fE Footer__icon___m4hTr Link__link___plGt2 SocialIcon__socialIcon___gm1fE Footer__icon___m4hTr" href="https://www.youtube.com/channel/UCso9-KdHZ6vfbYgM59zp9EA" tabindex="0" role="link" target="_blank" rel="noopener noreferrer" aria-label="https://www.youtube.com/channel/UCso9-KdHZ6vfbYgM59zp9EA"><i class="icon icon-youtube-new"></i></a></div></div></div><div class="Footer__copyrightContainer____MV8W"><div class="Footer__copyrightLayout___XD0J7"><p class="Paragraph__small___OZxzF">Copyright © <!-- -->2024<!-- --> scite LLC. All rights reserved.</p><p class="Paragraph__small___OZxzF">Made with 💙 for researchers</p><div class="Footer__rsssFamily___jPDL1"><p class="Footer__rsssBlurb___XhmEW Paragraph__small___OZxzF">Part of the Research Solutions Family.</p><img src="https://cdn.scite.ai/assets/images/logo-rs-black-new.png" class="Footer__rsssLogo___bG803"/></div></div></div></div><div style="position:fixed;z-index:9999"></div><!--/$--></div><div id="scite-tooltips"></div><script type="application/javascript">window.__SCITE_STORE_STATE = {"addReportDashboardModal":{"selectedPapers":[]},"ui":{"referralPartner":null,"freeReports":0,"bannerContent":null,"bannerClosed":false,"navMenu":{},"createDashboardFromSearchResultsModalShow":false,"savedSearchModalShow":false,"searchFilterModalShow":false,"flagModalShow":false,"resetPasswordModalShow":false,"loginModalShow":false,"referenceCheckModalShow":false,"deleteDashboardModalShow":false,"addReportToDashboardModalShow":false,"shareDashboardModalShow":false,"editDashboardModalShow":false,"upgradeModalShow":false,"exportReportModalShow":false,"exportReferenceModalShow":false,"generateCitationModalShow":false,"exportDashboardModalShow":false,"dashboardLimitErrorModalShow":false,"whatIsThisReportModalShow":false,"whatIsThisSearchModalShow":false,"whatIsAssistantModalShow":false,"trialOverModalShow":false,"activateTrialModalShow":false,"cancelTrialCheckoutModalShow":false,"cookieModalShow":false,"personaModalShow":false,"loggedOutModalShow":true,"modalFromContext":"","shownModals":[],"hasUser":false,"user":null,"ipLocationData":{"data":null,"error":false,"loading":false},"fetchingUser":false,"savingUser":false,"saveUserError":false,"onboardingLoadTracker":{"state":undefined},"userEntitlements":null,"entitlementsLoading":false,"referralsLoading":false,"pageError":null,"browser":null,"extensionLoaded":false,"organizationLicense":{"hasLicense":false},"linkResolver":null,"sickoMode":false,"authors":[],"navOpen":false,"showMobileSearch":false,"redeemCodeLoading":false,"redeemCodeError":null,"redeemCodeSuccess":false,"applyDiscountLoading":false,"applyDiscountError":null,"applyDiscountSuccess":false,"userDiscount":null,"search":{"term":"","focused":false,"autocompletesLoadTracker":{},"autocompletes":{}},"referencesToExport":[],"citeGeneratorPaperData":{},"dimensions":{},"cookiePreference":null,"userChurnKey":null,"churnKeyLoading":false,"fullTextLinkState":{},"agAvailabilityState":{},"agAvailabilityQueue":[]},"verifyEmail":{"loading":false,"verified":false,"expired":false},"dashboard":{"id":"","name":"","displayName":"","normalizedName":"","description":"","slug":"","dashboardType":"","accessType":"","isPublic":null,"componentLayout":[],"doiQuery":{},"journalMetadata":{},"affiliationMetadata":{},"institutionMetadata":{},"haveAccessToDashboard":null,"lastUpdated":null,"doisUpdatedTS":null,"doisRefreshedTS":null,"refreshStatus":"","loadState":{},"deleteDashboardError":false,"deletingDashboard":false,"totalDoiCount":0,"matchedDoiCount":0,"unmatchedDoiCount":0,"exportLoadTracker":{},"setDashboardUsersLoading":false,"setDashboardUsersError":false,"setDashboardUsersSuccess":false,"dashboardAccessList":null,"getDashboardAccessListLoading":false,"getDashboardAccessListSuccess":false,"getDashboardAccessListError":false},"notifications":{"notifications":[],"loading":false,"error":null,"notificationItems":[],"notificationItemsLoading":false,"notificationItemsError":null,"notificationItemsPage":1,"notificationItemsTotal":0,"newNotificationItems":0,"notificationItemsFilters":{},"dropDownNotificationItems":[],"dropDownNotificationItemsLoading":false,"dropDownNotificationItemsError":null,"notificationSetStatusLoading":false,"notificationSetStatusError":null},"report":{"paper":"10.4172\u002F2325-9701.s1-004","tally":"10.4172\u002F2325-9701.s1-004","citations":[{"id":2043017062,"source":"10.3390\u002Fcancers12020433","target":"10.4172\u002F2325-9701.s1-004","negative":0.02137692868709564,"positive":0.021889103576540947,"neutral":1,"section":"discussion","type":"mentioning","typeConfidence":1,"snippet":"On one hand, their activity as gatekeepers of adaptive immunity is needed \u003Ccite data-doi=\"10.1158\u002F1078-0432.ccr-18-0047\"\u003E[41]\u003C\u002Fcite\u003E, but on the other hand, an inflammatory T-cell phenotype boosts tumor progression. In GBM, the proinflammatory cytokines IL-17 and IL-22 have been identified as cancer-promoting molecules activating oncogenic STAT3 signaling, thereby protecting GBM cells from apoptosis, promoting GBM proliferation and enhancing invasion \u003Ccite data-doi=\"10.1371\u002Fjournal.pone.0119872\"\u003E[26,\u003C\u002Fcite\u003E\u003Ccite data-doi=\"10.4172\u002F2325-9701.s1-004\"\u003E27,\u003C\u002Fcite\u003E\u003Ccite data-doi=\"10.1111\u002Fjcmm.13938\"\u003E44]\u003C\u002Fcite\u003E. IL-22 plays a particularly important role in immune cell-tumor interactions, as it is solely secreted by immune cells and exerts its effects only on non-hematopoietic cells \u003Ccite data-doi=\"10.1002\u002Feji.201747183\"\u003E[45]\u003C\u002Fcite\u003E.","lang":"en","langConfidence":"0.9200000166893005","refLocation":"b26\u002F2","memberId":1968,"selfCites":[],"snippetHidden":false},{"id":2127694155,"source":"10.18632\u002Foncotarget.6847","target":"10.4172\u002F2325-9701.s1-004","negative":0.007567840442061424,"positive":0.05883057042956352,"neutral":1,"section":"discussion","type":"mentioning","typeConfidence":1,"snippet":"The cytokine profile as well as the type and density of immune cells in the tumor microenvironment have been shown to play a critical role in the progression of malignant tumors [ \u003Ccite data-doi=\"10.2217\u002F14796694.4.3.433\"\u003E 38 \u003C\u002Fcite\u003E – \u003Ccite data-doi=\"10.1126\u002Fscience.1129139\"\u003E 40 \u003C\u002Fcite\u003E ]. Our group and others have demonstrated the infiltration\u002Fenhancement of IL-17-producing cells in malignant gliomas [ \u003Ccite data-doi=\"10.1007\u002Fs00262-012-1312-7\"\u003E 32 \u003C\u002Fcite\u003E – \u003Ccite data-doi=\"10.1016\u002Fj.intimp.2011.03.015\"\u003E 34 \u003C\u002Fcite\u003E , \u003Ccite data-doi=\"10.1371\u002Fjournal.pone.0015390\"\u003E 36 \u003C\u002Fcite\u003E ] and IL-17 has been linked to cancer progression in many tumor types [ \u003Ccite data-doi=\"10.4172\u002F2325-9701.s1-004\"\u003E 33 \u003C\u002Fcite\u003E , \u003Ccite data-doi=\"10.1002\u002Fijc.24497\"\u003E 41 \u003C\u002Fcite\u003E – \u003Ccite data-doi=\"10.1177\u002F147323001003800223\"\u003E 44 \u003C\u002Fcite\u003E ]. IL-17 over-expression potentially enhance glioma cell growth in vivo , which may be associated with accelerated angiogenesis [ \u003Ccite data-doi=\"10.3892\u002Fol.2013.1518\"\u003E 45 \u003C\u002Fcite\u003E ].","lang":"en","langConfidence":"0.9200000166893005","refLocation":"r33\u002F1","memberId":7892,"selfCites":[{"type":"SHAREDAUTHOR","family":"Parajuli","given":"Prahlad"}],"snippetHidden":false},{"id":2127694162,"source":"10.18632\u002Foncotarget.6847","target":"10.4172\u002F2325-9701.s1-004","negative":0.0005303756450302898,"positive":0.00046132641728036106,"neutral":1,"section":"discussion","type":"mentioning","typeConfidence":1,"snippet":"More importantly, both these studies did not analyze the status of IL-17R expression in the tumor cells. Overall, the role of IL-17 in glioma progression remains uncertain and the precise underlying mechanisms remain largely unknown [ \u003Ccite data-doi=\"10.4172\u002F2325-9701.s1-004\"\u003E 33 \u003C\u002Fcite\u003E ]. In the current study, we have demonstrated a potential impact of IL-17-IL-17R interaction in glioma growth and progression via direct stimulation of the GSCs.","lang":"en","langConfidence":"0.8899999856948853","refLocation":"r33\u002F2","memberId":7892,"selfCites":[{"type":"SHAREDAUTHOR","family":"Parajuli","given":"Prahlad"}],"snippetHidden":false},{"id":2127694165,"source":"10.18632\u002Foncotarget.6847","target":"10.4172\u002F2325-9701.s1-004","negative":0.01038370057940483,"positive":0.032127439975738525,"neutral":1,"section":"discussion","type":"mentioning","typeConfidence":1,"snippet":"GSCs were first identified and purified from human brain tumors by Singh et al as a population of CD133 + tumor cells [ 49 , \u003Ccite data-doi=\"10.1038\u002Fnature03128\"\u003E 50 \u003C\u002Fcite\u003E ]. While several studies have reaffirmed strong association of CD133 with GSCs, the intermediate filament protein Nestin and the transcription factor Sox2 have also often been reported in GSCs [ \u003Ccite data-doi=\"10.1016\u002Fj.cell.2014.02.030\"\u003E 8 \u003C\u002Fcite\u003E , \u003Ccite data-doi=\"10.4172\u002F2325-9701.s1-004\"\u003E 33 \u003C\u002Fcite\u003E , \u003Ccite data-doi=\"10.3748\u002Fwjg.v17.i4.409\"\u003E 51 \u003C\u002Fcite\u003E – \u003Ccite data-doi=\"10.1002\u002Fijc.24402\"\u003E 54 \u003C\u002Fcite\u003E ]. Sox2 plays a critical role in the induction or maintenance of glioma ‘stemness’ [ \u003Ccite data-doi=\"10.1016\u002Fj.cell.2014.02.030\"\u003E 8 \u003C\u002Fcite\u003E , \u003Ccite data-doi=\"10.1074\u002Fjbc.m111.300863\"\u003E 55 \u003C\u002Fcite\u003E ].","lang":"en","langConfidence":"0.949999988079071","refLocation":"r33\u002F3","memberId":7892,"selfCites":[{"type":"SHAREDAUTHOR","family":"Parajuli","given":"Prahlad"}],"snippetHidden":false},{"id":2043017032,"source":"10.3390\u002Fcancers12020433","target":"10.4172\u002F2325-9701.s1-004","negative":0.003098056465387344,"positive":0.0021462026052176952,"neutral":1,"section":"anakinra reduced inflammatory signaling in lymphocytes co-cu","type":"mentioning","typeConfidence":1,"snippet":"We assumed that anakinra might also affect these aspects of tumor-associated inflammation. We thus extracted T cells after indirect co-culture of PBMCs and GBM cells and analyzed expression levels of inflammatory cytokines that were (a) secreted by T cells and (b) involved in oncogenic signaling \u003Ccite data-doi=\"10.1073\u002Fpnas.1705165114\"\u003E[25]\u003C\u002Fcite\u003E\u003Ccite data-doi=\"10.1371\u002Fjournal.pone.0119872\"\u003E[26]\u003C\u002Fcite\u003E\u003Ccite data-doi=\"10.4172\u002F2325-9701.s1-004\"\u003E[27]\u003C\u002Fcite\u003E. After administration of anakinra, we detected a marked decrease of proinflammatory IFNγ, IL-17, and IL-22 mRNA expression ( Figure 5A: IFNγ: −85.0% ± 45.4%, IL-17: −88.1% ± 21.7%, IL-22: −63.2% ± 22.0%, n = 13, p < 0.004) in these T cells as well as reduced protein levels in the respective conditioned medium ( Figure 5A: IFNγ: −13.04% ±3.3, IL-17: −51.8% ± 20.8%, IL-22: −37.1% ± 8.5%, n = 10, p < 0.004).","lang":"en","langConfidence":"0.9399999976158142","refLocation":"b26\u002F1","memberId":1968,"selfCites":[],"snippetHidden":false},{"source":"10.1038\u002Fs41419-022-05514-0","target":"10.4172\u002F2325-9701.s1-004","selfCites":[],"dataSource":"KALA"},{"source":"10.1038\u002Fs41590-020-00860-7","target":"10.4172\u002F2325-9701.s1-004","selfCites":[],"dataSource":"CR"},{"source":"10.1038\u002Fs43018-023-00547-6","target":"10.4172\u002F2325-9701.s1-004","selfCites":[],"dataSource":"CR"},{"source":"10.1080\u002F14786419.2022.2063856","target":"10.4172\u002F2325-9701.s1-004","selfCites":[],"dataSource":"KALA"},{"source":"10.1093\u002Fneuonc\u002Fnoac154","target":"10.4172\u002F2325-9701.s1-004","selfCites":[],"dataSource":"OPENALEX"}],"citationTallies":{"10.3390\u002Fcancers12020433":{"total":12,"supporting":0,"contradicting":0,"mentioning":12,"unclassified":0,"doi":"10.3390\u002Fcancers12020433","citingPublications":16},"10.18632\u002Foncotarget.6847":{"total":24,"supporting":0,"contradicting":0,"mentioning":24,"unclassified":0,"doi":"10.18632\u002Foncotarget.6847","citingPublications":34},"10.1038\u002Fs41419-022-05514-0":{"total":8,"supporting":0,"contradicting":0,"mentioning":8,"unclassified":0,"doi":"10.1038\u002Fs41419-022-05514-0","citingPublications":23},"10.1038\u002Fs41590-020-00860-7":{"total":73,"supporting":5,"contradicting":0,"mentioning":68,"unclassified":0,"doi":"10.1038\u002Fs41590-020-00860-7","citingPublications":93},"10.1038\u002Fs43018-023-00547-6":{"total":7,"supporting":0,"contradicting":0,"mentioning":7,"unclassified":0,"doi":"10.1038\u002Fs43018-023-00547-6","citingPublications":35},"10.1080\u002F14786419.2022.2063856":{"total":9,"supporting":0,"contradicting":0,"mentioning":9,"unclassified":0,"doi":"10.1080\u002F14786419.2022.2063856","citingPublications":7},"10.1093\u002Fneuonc\u002Fnoac154":{"total":18,"supporting":0,"contradicting":0,"mentioning":18,"unclassified":0,"doi":"10.1093\u002Fneuonc\u002Fnoac154","citingPublications":28}},"metadata":{"totalCitationCount":26,"restrictedCitationCount":5,"distinctSourceCount":19},"papers":{"10.3390\u002Fcancers12020433":{"id":9294799143,"doi":"10.3390\u002Fcancers12020433","slug":"the-il-1-antagonist-anakinra-attenuates-mOLnMEre","type":"journal-article","title":"The IL-1 Antagonist Anakinra Attenuates Glioblastoma Aggressiveness by Dampening Tumor-Associated Inflammation","abstract":"Background: The recombinant IL-1 receptor antagonist anakinra—currently approved for the treatment of autoinflammatory diseases—blocks IL-1β-mediated inflammatory signaling. As inflammation is a major driver of cancer, we hypothesized that anakinra might be able to mitigate glioblastoma (GBM) aggressiveness. Methods: Primary GBM or T98G cells were incubated alone or with peripheral blood mononuclear cells (PBMCs) and were subsequently treated with IL-1β and\u002For anakinra. T cells were obtained by magnetic bead isolation. Protein and mRNA expression were quantified by SDS-PAGE, qRT-PCR, and ELISA, respectively. Cell proliferation and apoptosis were analyzed via flow cytometry. Chemotaxis was studied via time-lapse microscopy. Results: Upon IL-1β stimulation, anakinra attenuated proinflammatory gene expression in both GBM cells and PBMCs, and mitigated tumor migration and proliferation. In a more lifelike model replacing IL-1β stimulation by GBM–PBMC co-culture, sole presence of PBMCs proved sufficient to induce a proinflammatory phenotype in GBM cells with enhanced proliferation and migration rates and attenuated apoptosis. Anakinra antagonized these pro-tumorigenic effects and, moreover, reduced inflammatory signaling in T cells without compromising anti-tumor effector molecules. Conclusion: By dampening the inflammatory crosstalk between GBM and immune cells, anakinra mitigated GBM aggressiveness. Hence, counteracting IL-1β-mediated inflammation might be a promising strategy to pursue.","authors":[{"family":"Hübner","given":"Max","affiliation":"LMU Klinikum","authorSlug":"max-hubner-4LjZO3","authorName":"Max Hübner","authorID":"7246942","authorLastKnownAffiliationId":14015,"authorSequenceNumber":1,"affiliationSlug":"lmu-klinikum-bNQp","affiliationID":"14015"},{"family":"Effinger","given":"David","affiliation":"LMU Klinikum","authorSlug":"david-effinger-WxN6ed","authorName":"David Effinger","authorID":"11947904","authorLastKnownAffiliationId":11606,"authorSequenceNumber":2,"affiliationSlug":"lmu-klinikum-bNQp","affiliationID":"14015"},{"family":"Wang","given":"Tingting","affiliation":"LMU Klinikum","authorSlug":"tingting-wang-D1z1RP","authorName":"Tingting Wang","authorID":"5709519","authorLastKnownAffiliationId":26472,"authorSequenceNumber":3,"affiliationSlug":"lmu-klinikum-bNQp","affiliationID":"14015"},{"family":"Strauß","given":"Gabriele","affiliation":"LMU Klinikum","authorSlug":"gabriele-strauss-1ZJgJ0","authorName":"Gabriele Strauß","authorID":"4774747","authorLastKnownAffiliationId":210631,"authorSequenceNumber":4,"affiliationSlug":"lmu-klinikum-bNQp","affiliationID":"14015"},{"family":"Pogoda","given":"Kristin","affiliation":"Ludwig-Maximilians-Universität München","authorSlug":"kristin-pogoda-jMLYXM","authorName":"Kristin Pogoda","authorID":"7488581","authorLastKnownAffiliationId":217602,"authorSequenceNumber":5,"affiliationSlug":"ludwig-maximilians-universitat-munchen-z1r6","affiliationID":"11606"},{"family":"Kreth","given":"Friedrich-Wilhelm","affiliation":"LMU Klinikum","authorSlug":"friedrich-wilhelm-kreth-jMrWA4","authorName":"Friedrich-Wilhelm Kreth","authorID":"6117537","authorLastKnownAffiliationId":11606,"authorSequenceNumber":6,"affiliationSlug":"lmu-klinikum-bNQp","affiliationID":"14015"},{"family":"Kreth","given":"Simone","affiliation":"LMU Klinikum","authorSlug":"simone-kreth-EWJgVG","authorName":"Simone Kreth","authorID":"4681817","authorLastKnownAffiliationId":11606,"authorSequenceNumber":7,"affiliationSlug":"lmu-klinikum-bNQp","affiliationID":"14015"}],"keywords":["glioblastoma","inflammation","IL-1β","anakinra"],"year":2020,"shortJournal":"Cancers","publisher":"MDPI AG","issue":"2","volume":"12","page":"433","retracted":false,"memberId":1968,"issns":["2072-6694"],"editorialNotices":[],"journalSlug":"cancers-dvlO3","journal":"Cancers","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},"10.18632\u002Foncotarget.6847":{"id":119866002,"doi":"10.18632\u002Foncotarget.6847","slug":"preferential-expression-of-functional-il-17r-9QwNpE","type":"journal-article","title":"Preferential expression of functional IL-17R in glioma stem cells: potential role in self-renewal","abstract":"Gliomas are the most common primary brain tumor and one of the most lethal solid tumors. Mechanistic studies into identification of novel biomarkers are needed to develop new therapeutic strategies for this deadly disease. The objective for this study was to explore the potential direct impact of IL-17−IL-17R interaction in gliomas. Immunohistochemistry and flow cytometry analysis of 12 tumor samples obtained from patients with high grade gliomas revealed that a considerable population (2–19%) of cells in all malignant gliomas expressed IL-17RA, with remarkable co-expression of the glioma stem cell (GSC) markers CD133, Nestin, and Sox2. IL-17 enhanced the self-renewal of GSCs as determined by proliferation and Matrigel® colony assays. IL-17 also induced cytokine\u002Fchemokine (IL-6, IL-8, interferon-γ-inducible protein [IP-10], and monocyte chemoattractant protein-1 [MCP-1]) secretion in GSCs, which were differentially blocked by antibodies against IL-17R and IL-6R. Western blot analysis showed that IL-17 modulated the activity of signal transducer and activator of transcription 3 (STAT3), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), glycogen synthase kinase-3β (GSK-3β) and β-catenin in GSCs. While IL-17R-mediated secretion of IL-6 and IL-8 were significantly blocked by inhibitors of NF-κB and STAT3; NF-κB inhibitor was more potent than STAT3 inhibitor in blocking IL-17-induced MCP-1 secretion. Overall, our results suggest that IL-17–IL-17R interaction in GSCs induces an autocrine\u002Fparacrine cytokine feedback loop, which may provide an important signaling component for maintenance\u002Fself-renewal of GSCs via constitutive activation of both NF-κB and STAT3. The results also strongly implicate IL-17R as an important functional biomarker for therapeutic targeting of GSCs.","authors":[{"family":"Parajuli","given":"Prahlad","affiliation":"Karmanos Cancer Institute","authorSlug":"prahlad-parajuli-5Gl4gV","authorName":"Prahlad Parajuli","authorID":"5474125","authorLastKnownAffiliationId":11741,"authorSequenceNumber":1,"affiliationSlug":"karmanos-cancer-institute-G5z6L","affiliationID":"170613"},{"family":"Anand","given":"Rohit","affiliation":"Karmanos Cancer Institute","authorSlug":"rohit-anand-PQkgaR","authorName":"Rohit Anand","authorID":"7258445","authorLastKnownAffiliationId":4831,"authorSequenceNumber":2,"affiliationSlug":"karmanos-cancer-institute-G5z6L","affiliationID":"170613"},{"family":"Mandalaparty","given":"Chandramouli","affiliation":"Karmanos Cancer Institute","authorSlug":"chandramouli-mandalaparty-aMOOK","authorName":"Chandramouli Mandalaparty","authorID":"3397439","authorLastKnownAffiliationId":7761,"authorSequenceNumber":3,"affiliationSlug":"karmanos-cancer-institute-G5z6L","affiliationID":"170613"},{"family":"Suryadevara","given":"Raviteja","affiliation":"Karmanos Cancer Institute","authorSlug":"raviteja-suryadevara-1OPOX","authorName":"Raviteja Suryadevara","authorID":"3558247","authorLastKnownAffiliationId":11691,"authorSequenceNumber":4,"affiliationSlug":"karmanos-cancer-institute-G5z6L","affiliationID":"170613"},{"family":"Sriranga","given":"Preethi U.","affiliation":"Karmanos Cancer Institute","authorSlug":"preethi-u-sriranga-vyzawV","authorName":"Preethi U. Sriranga","authorID":"10462597","authorLastKnownAffiliationId":11741,"authorSequenceNumber":5,"affiliationSlug":"karmanos-cancer-institute-G5z6L","affiliationID":"170613"},{"family":"Michelhaugh","given":"Sharon K.","affiliation":"Karmanos Cancer Institute","authorSlug":"sharon-k-michelhaugh-PbMJ2","authorName":"Sharon K. Michelhaugh","authorID":"1168145","authorLastKnownAffiliationId":284809,"authorSequenceNumber":6,"affiliationSlug":"karmanos-cancer-institute-G5z6L","affiliationID":"170613"},{"family":"Cazacu","given":"Simona","affiliation":"Henry Ford Hospital","authorSlug":"simona-cazacu-1ZMGlE","authorName":"Simona Cazacu","authorID":"6437147","authorLastKnownAffiliationId":11691,"authorSequenceNumber":7,"affiliationSlug":"henry-ford-hospital-1DZM","affiliationID":"11691"},{"family":"Finniss","given":"Susan","affiliation":"Henry Ford Hospital","authorSlug":"susan-finniss-V0gnvK","authorName":"Susan Finniss","authorID":"6458982","authorLastKnownAffiliationId":11691,"authorSequenceNumber":8,"affiliationSlug":"henry-ford-hospital-1DZM","affiliationID":"11691"},{"family":"Thakur","given":"Archana","affiliation":"Karmanos Cancer Institute","authorSlug":"archana-thakur-1ZYymE","authorName":"Archana Thakur","authorID":"4652947","authorLastKnownAffiliationId":26257,"authorSequenceNumber":9,"affiliationSlug":"karmanos-cancer-institute-G5z6L","affiliationID":"170613"},{"family":"Lum","given":"Lawrence G.","affiliation":"Wayne State University","authorSlug":"lawrence-g-lum-b2mzXR","authorName":"Lawrence G. Lum","authorID":"5223359","authorLastKnownAffiliationId":26257,"authorSequenceNumber":10,"affiliationSlug":"wayne-state-university-Xje9","affiliationID":"11741"},{"family":"Schalk","given":"Dana","affiliation":"Karmanos Cancer Institute","authorSlug":"dana-schalk-VKeKNj","authorName":"Dana Schalk","authorID":"8524038","authorLastKnownAffiliationId":26257,"authorSequenceNumber":11,"affiliationSlug":"karmanos-cancer-institute-G5z6L","affiliationID":"170613"},{"family":"Brodie","given":"Chaya","affiliation":"Henry Ford Hospital","authorSlug":"chaya-brodie-V0zagP","authorName":"Chaya Brodie","authorID":"5970082","authorLastKnownAffiliationId":8374,"authorSequenceNumber":12,"affiliationSlug":"henry-ford-hospital-1DZM","affiliationID":"11691"},{"family":"Mittal","given":"Sandeep","affiliation":"Karmanos Cancer Institute","authorSlug":"sandeep-mittal-8GXGxY","authorName":"Sandeep Mittal","authorID":"6136321","authorLastKnownAffiliationId":140389,"authorSequenceNumber":13,"affiliationSlug":"karmanos-cancer-institute-G5z6L","affiliationID":"170613"}],"keywords":["Research Paper"],"year":2016,"shortJournal":"Oncotarget","publisher":"Impact Journals, LLC","issue":"5","volume":"7","page":"6121-6135","retracted":false,"memberId":7892,"issns":["1949-2553"],"editorialNotices":[],"journalSlug":"oncotarget-lZQVv","journal":"Oncotarget","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},"10.1038\u002Fs41419-022-05514-0":{"id":11613513975,"doi":"10.1038\u002Fs41419-022-05514-0","slug":"dc-vaccines-loaded-with-glioma-ZG61RgPg","type":"journal-article","title":"DC vaccines loaded with glioma cells killed by photodynamic therapy induce Th17 anti-tumor immunity and provide a four-gene signature for glioma prognosis","abstract":"Gliomas, the most frequent type of primary tumor of the central nervous system in adults, results in significant morbidity and mortality. Despite the development of novel, complex, multidisciplinary, and targeted therapies, glioma therapy has not progressed much over the last decades. Therefore, there is an urgent need to develop novel patient-adjusted immunotherapies that actively stimulate antitumor T cells, generate long-term memory, and result in significant clinical benefits. This work aimed to investigate the efficacy and molecular mechanism of dendritic cell (DC) vaccines loaded with glioma cells undergoing immunogenic cell death (ICD) induced by photosens-based photodynamic therapy (PS-PDT) and to identify reliable prognostic gene signatures for predicting the overall survival of patients. Analysis of the transcriptional program of the ICD-based DC vaccine led to the identification of robust induction of Th17 signature when used as a vaccine. These DCs demonstrate retinoic acid receptor-related orphan receptor-γt dependent efficacy in an orthotopic mouse model. Moreover, comparative analysis of the transcriptome program of the ICD-based DC vaccine with transcriptome data from the TCGA-LGG dataset identified a four-gene signature (CFH, GALNT3, SMC4, VAV3) associated with overall survival of glioma patients. This model was validated on overall survival of CGGA-LGG, TCGA-GBM, and CGGA-GBM datasets to determine whether it has a similar prognostic value. To that end, the sensitivity and specificity of the prognostic model for predicting overall survival were evaluated by calculating the area under the curve of the time-dependent receiver operating characteristic curve. The values of area under the curve for TCGA-LGG, CGGA-LGG, TCGA-GBM, and CGGA-GBM for predicting five-year survival rates were, respectively, 0.75, 0.73, 0.9, and 0.69. These data open attractive prospects for improving glioma therapy by employing ICD and PS-PDT-based DC vaccines to induce Th17 immunity and to use this prognostic model to predict the overall survival of glioma patients.","authors":[{"family":"Vedunova","given":"Maria","affiliation":"N. I. Lobachevsky State University of Nizhny Novgorod","authorSlug":"maria-vedunova-EWz6k1","authorName":"Maria Vedunova","authorID":"7062761","authorLastKnownAffiliationId":26154,"authorSequenceNumber":1,"affiliationSlug":"n-i-lobachevsky-state-university-6Dk1","affiliationID":"26154"},{"family":"Turubanova","given":"Victoria D.","affiliation":"N. I. Lobachevsky State University of Nizhny Novgorod","authorSlug":"victoria-d-turubanova-ay18dp","authorName":"Victoria D. Turubanova","authorID":"8783139","authorLastKnownAffiliationId":26154,"authorSequenceNumber":2,"affiliationSlug":"n-i-lobachevsky-state-university-6Dk1","affiliationID":"26154"},{"family":"Vershinina","given":"O. S.","affiliation":"N. I. Lobachevsky State University of Nizhny Novgorod","authorSlug":"o-s-vershinina-wZYJ6a","authorName":"O. S. Vershinina","authorID":"14224928","authorLastKnownAffiliationId":26154,"authorSequenceNumber":3,"affiliationSlug":"n-i-lobachevsky-state-university-6Dk1","affiliationID":"26154"},{"family":"Savyuk","given":"Maria","affiliation":"N. I. Lobachevsky State University of Nizhny Novgorod","authorSlug":"maria-savyuk-kvGgzJ","authorName":"Maria Savyuk","authorID":"12562468","authorLastKnownAffiliationId":26154,"authorSequenceNumber":4,"affiliationSlug":"n-i-lobachevsky-state-university-6Dk1","affiliationID":"26154"},{"family":"Efimova","given":"Iuliia","affiliation":"Ghent University","authorSlug":"iuliia-efimova-vJm9R4","authorName":"Iuliia Efimova","authorID":"7338097","authorLastKnownAffiliationId":143656,"authorSequenceNumber":5,"affiliationSlug":"ghent-university-9pwE","affiliationID":"23202"},{"family":"Mishchenko","given":"Tatiana A.","affiliation":"N. I. Lobachevsky State University of Nizhny Novgorod","authorSlug":"tatiana-a-mishchenko-6MZAkg","authorName":"Tatiana A. Mishchenko","authorID":"7568798","authorLastKnownAffiliationId":26154,"authorSequenceNumber":6,"affiliationSlug":"n-i-lobachevsky-state-university-6Dk1","affiliationID":"26154"},{"family":"Raedt","given":"Robrecht","affiliation":"Ghent University","authorSlug":"robrecht-raedt-n6xDRN","authorName":"Robrecht Raedt","authorID":"4610877","authorLastKnownAffiliationId":23202,"authorSequenceNumber":7,"affiliationSlug":"ghent-university-9pwE","affiliationID":"23202"},{"family":"Vral","given":"Anne","affiliation":"Ghent University","authorSlug":"anne-vral-K6de15","authorName":"Anne Vral","authorID":"5397035","authorLastKnownAffiliationId":23202,"authorSequenceNumber":8,"affiliationSlug":"ghent-university-9pwE","affiliationID":"23202"},{"family":"Vanhove","given":"Christian","affiliation":"Ghent University","authorSlug":"christian-vanhove-GV2X1","authorName":"Christian Vanhove","authorID":"1037013","authorLastKnownAffiliationId":23202,"authorSequenceNumber":9,"affiliationSlug":"ghent-university-9pwE","affiliationID":"23202"},{"family":"Korsakova","given":"Daria","affiliation":"N. I. Lobachevsky State University of Nizhny Novgorod","authorSlug":"daria-korsakova-1DwY6j","authorName":"Daria Korsakova","authorID":"24723747","authorLastKnownAffiliationId":26154,"authorSequenceNumber":10,"affiliationSlug":"n-i-lobachevsky-state-university-6Dk1","affiliationID":"26154"},{"family":"Bachert","given":"Claus","affiliation":"Ghent University","authorSlug":"claus-bachert-0GvaVZ","authorName":"Claus Bachert","authorID":"5712556","authorLastKnownAffiliationId":140506,"authorSequenceNumber":11,"affiliationSlug":"ghent-university-9pwE","affiliationID":"23202"},{"family":"Coppieters","given":"Frauke","affiliation":"Ghent University Hospital","authorSlug":"frauke-coppieters-lZzGmm","authorName":"Frauke Coppieters","authorID":"6766680","authorLastKnownAffiliationId":15531,"authorSequenceNumber":12,"affiliationSlug":"ghent-university-hospital-ZVQM","affiliationID":"15531"},{"family":"Agostinis","given":"Patrizia","affiliation":"KU Leuven","authorSlug":"patrizia-agostinis-2MgRm","authorName":"Patrizia Agostinis","authorID":"935376","authorLastKnownAffiliationId":184860,"authorSequenceNumber":13,"affiliationSlug":"ku-leuven-5YeG","affiliationID":"4225"},{"family":"Garg","given":"Abhishek D.","affiliation":"KU Leuven","authorSlug":"abhishek-d-garg-n6dNXD","authorName":"Abhishek D. Garg","authorID":"4912033","authorLastKnownAffiliationId":4225,"authorSequenceNumber":14,"affiliationSlug":"ku-leuven-5YeG","affiliationID":"4225"},{"family":"Ivanchenko","given":"Mikhail","affiliation":"N. I. Lobachevsky State University of Nizhny Novgorod","authorSlug":"mikhail-ivanchenko-dv8Yab","authorName":"Mikhail Ivanchenko","authorID":"6514318","authorLastKnownAffiliationId":26154,"authorSequenceNumber":15,"affiliationSlug":"n-i-lobachevsky-state-university-6Dk1","affiliationID":"26154"},{"family":"Krysko","given":"Olga","affiliation":"Ghent University","authorSlug":"olga-krysko-6OxW9","authorName":"Olga Krysko","authorID":"1021998","authorLastKnownAffiliationId":23202,"authorSequenceNumber":16,"affiliationSlug":"ghent-university-9pwE","affiliationID":"23202"},{"family":"Krysko","given":"Dmitri V.","affiliation":"N. I. Lobachevsky State University of Nizhny Novgorod","authorSlug":"dmitri-v-krysko-G3em6J","authorName":"Dmitri V. Krysko","authorID":"5835357","authorLastKnownAffiliationId":143656,"authorSequenceNumber":17,"affiliationSlug":"n-i-lobachevsky-state-university-6Dk1","affiliationID":"26154"}],"keywords":["\n Article\n "],"year":2022,"shortJournal":"Cell Death Dis","publisher":"Springer Science and Business Media LLC","issue":"12","volume":"13","memberId":297,"issns":["2041-4889"],"editorialNotices":[],"journalSlug":"cell-death-and-disease-zRQY3","journal":"Cell Death &Amp; Disease","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},"10.1038\u002Fs41590-020-00860-7":{"id":10150249912,"doi":"10.1038\u002Fs41590-020-00860-7","slug":"tumor-hypoxia-represses-γδ-t-0Gd093V8","type":"journal-article","title":"Tumor hypoxia represses γδ T cell-mediated antitumor immunity against brain tumors","authors":[{"family":"Park","given":"Jang Hyun","affiliation":"Korea Advanced Institute of Science and Technology","authorSlug":"jang-hyun-park-d3XQNd","authorName":"Jang Hyun Park","authorID":"7550718","authorLastKnownAffiliationId":13327,"authorSequenceNumber":1,"affiliationSlug":"korea-advanced-institute-of-science-NWbw","affiliationID":"13327"},{"family":"Kim","given":"Hyun‐Jin","affiliation":"Korea Advanced Institute of Science and Technology","authorSlug":"hyun-jin-kim-4LQgVw","authorName":"Hyun‐Jin Kim","authorID":"5830642","authorLastKnownAffiliationId":5489,"authorSequenceNumber":2,"affiliationSlug":"korea-advanced-institute-of-science-NWbw","affiliationID":"13327"},{"family":"Kim","given":"Chae Won","affiliation":"Korea Advanced Institute of Science and Technology","authorSlug":"chae-won-kim-6M2AgM","authorName":"Chae Won Kim","authorID":"9356954","authorLastKnownAffiliationId":139604,"authorSequenceNumber":3,"affiliationSlug":"korea-advanced-institute-of-science-NWbw","affiliationID":"13327"},{"family":"Kim","given":"Hyeon‐Cheol","affiliation":"Korea Advanced Institute of Science and Technology","authorSlug":"hyeon-cheol-kim-J1Pva6","authorName":"Hyeon‐Cheol Kim","authorID":"5459667","authorLastKnownAffiliationId":13327,"authorSequenceNumber":4,"affiliationSlug":"korea-advanced-institute-of-science-NWbw","affiliationID":"13327"},{"family":"Jung","given":"Yong-Taek","affiliation":"Korea Advanced Institute of Science and Technology","authorSlug":"yong-taek-jung-jMxlzd","authorName":"Yong-Taek Jung","authorID":"6174137","authorLastKnownAffiliationId":6972,"authorSequenceNumber":5,"affiliationSlug":"korea-advanced-institute-of-science-NWbw","affiliationID":"13327"},{"family":"Lee","given":"Hyunsoo","affiliation":"Korea Advanced Institute of Science and Technology","authorSlug":"hyunsoo-lee-J1PJnk","authorName":"Hyunsoo Lee","authorID":"5452123","authorLastKnownAffiliationId":22348,"authorSequenceNumber":6,"affiliationSlug":"korea-advanced-institute-of-science-NWbw","affiliationID":"13327"},{"family":"Lee","given":"Yunah","affiliation":"Korea Advanced Institute of Science and Technology","authorSlug":"yunah-lee-YDgY03","authorName":"Yunah Lee","authorID":"11434451","authorLastKnownAffiliationId":21339,"authorSequenceNumber":7,"affiliationSlug":"korea-advanced-institute-of-science-NWbw","affiliationID":"13327"},{"family":"Ju","given":"Young Seok","affiliation":"Korea Advanced Institute of Science and Technology","authorSlug":"young-seok-ju-9paOk","authorName":"Young Seok Ju","authorID":"970002","authorLastKnownAffiliationId":13327,"authorSequenceNumber":8,"affiliationSlug":"korea-advanced-institute-of-science-NWbw","affiliationID":"13327"},{"family":"Oh","given":"Ji Eun","affiliation":"Korea Advanced Institute of Science and Technology","authorSlug":"ji-eun-oh-y8WbPr","authorName":"Ji Eun Oh","authorID":"5162020","authorLastKnownAffiliationId":24204,"authorSequenceNumber":9,"affiliationSlug":"korea-advanced-institute-of-science-NWbw","affiliationID":"13327"},{"family":"Park","given":"Sung-Hong","affiliation":"Korea Advanced Institute of Science and Technology","authorSlug":"sung-hong-park-ZGvjkM","authorName":"Sung-Hong Park","authorID":"6571575","authorLastKnownAffiliationId":16275,"authorSequenceNumber":10,"affiliationSlug":"korea-advanced-institute-of-science-NWbw","affiliationID":"13327"},{"family":"Lee","given":"Jehee","affiliation":"Korea Advanced Institute of Science and Technology","authorSlug":"jehee-lee-wmkEK9","authorName":"Jehee Lee","authorID":"5776072","authorLastKnownAffiliationId":26736,"authorSequenceNumber":11,"affiliationSlug":"korea-advanced-institute-of-science-NWbw","affiliationID":"13327"},{"family":"Lee","given":"Sung Ki","affiliation":"Konyang University","authorSlug":"sung-ki-lee-V0AgDO","authorName":"Sung Ki Lee","authorID":"6620738","authorLastKnownAffiliationId":17386,"authorSequenceNumber":12,"affiliationSlug":"konyang-university-4vdl","affiliationID":"17386"},{"family":"Lee","given":"Kyung-Mi","affiliation":"Korea Advanced Institute of Science and Technology","authorSlug":"kyung-mi-lee-ZG5M0g","authorName":"Kyung-Mi Lee","authorID":"5877275","authorLastKnownAffiliationId":13327,"authorSequenceNumber":13,"affiliationSlug":"korea-advanced-institute-of-science-NWbw","affiliationID":"13327"}],"year":2021,"shortJournal":"Nat Immunol","publisher":"Springer Science and Business Media LLC","issue":"3","volume":"22","page":"336-346","memberId":297,"issns":["1529-2908","1529-2916"],"editorialNotices":[],"journalSlug":"nature-immunology-4LwkM","journal":"Nature Immunology","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},"10.1038\u002Fs43018-023-00547-6":{"id":11646835932,"doi":"10.1038\u002Fs43018-023-00547-6","slug":"cd103-regulatory-t-cells-underlie-2Nw8a8xx","type":"journal-article","title":"CD103+ regulatory T cells underlie resistance to radio-immunotherapy and impair CD8+ T cell activation in glioblastoma","abstract":"Glioblastomas are aggressive primary brain tumors with an inherent resistance to T cell-centric immunotherapy due to their low mutational burden and immunosuppressive tumor microenvironment. Here we report that fractionated radiotherapy of preclinical glioblastoma models induce a tenfold increase in T cell content. Orthogonally, spatial imaging mass cytometry shows T cell enrichment in human recurrent tumors compared with matched primary glioblastoma. In glioblastoma-bearing mice, α-PD-1 treatment applied at the peak of T cell infiltration post-radiotherapy results in a modest survival benefit compared with concurrent α-PD-1 administration. Following α-PD-1 therapy, CD103+ regulatory T cells (Tregs) with upregulated lipid metabolism accumulate in the tumor microenvironment, and restrain immune checkpoint blockade response by repressing CD8+ T cell activation. Treg targeting elicits tertiary lymphoid structure formation, enhances CD4+ and CD8+ T cell frequency and function and unleashes radio-immunotherapeutic efficacy. These results support the rational design of therapeutic regimens limiting the induction of immunosuppressive feedback pathways in the context of T cell immunotherapy in glioblastoma.","authors":[{"family":"Hooren","given":"Luuk van","affiliation":"Oncode Institute","authorSlug":"luuk-van-hooren-ZxrjPP","authorName":"Luuk van Hooren","authorID":"9809531","authorLastKnownAffiliationId":183,"authorSequenceNumber":1,"affiliationSlug":"oncode-institute-A3k92","affiliationID":"146893"},{"family":"Handgraaf","given":"Shanna M.","affiliation":"Oncode Institute","authorSlug":"shanna-m-handgraaf-3803PA","authorName":"Shanna M. Handgraaf","authorID":"9491988","authorLastKnownAffiliationId":147273,"authorSequenceNumber":2,"affiliationSlug":"oncode-institute-A3k92","affiliationID":"146893"},{"family":"Kloosterman","given":"Daan J.","affiliation":"Oncode Institute","authorSlug":"daan-j-kloosterman-bj3eDW","authorName":"Daan J. Kloosterman","authorID":"15539759","authorLastKnownAffiliationId":147273,"authorSequenceNumber":3,"affiliationSlug":"oncode-institute-A3k92","affiliationID":"146893"},{"family":"Karimi","given":"Elham","affiliation":"McGill University Health Centre","authorSlug":"elham-karimi-n688nr","authorName":"Elham Karimi","authorID":"7146733","authorLastKnownAffiliationId":16282,"authorSequenceNumber":4,"affiliationSlug":"mcgill-university-health-centre-VLEK","affiliationID":"16282"},{"family":"Mil","given":"Lotte W H G van","affiliation":"Oncode Institute","authorSlug":"lotte-w-h-g-van-1ZbL0","authorName":"Lotte W H G van Mil","authorID":"134903","authorLastKnownAffiliationId":147273,"authorSequenceNumber":5,"affiliationSlug":"oncode-institute-A3k92","affiliationID":"146893"},{"family":"Gassama","given":"Awa A","affiliation":"Oncode Institute","authorSlug":"awa-a-gassama-Ml8EGY","authorName":"Awa A Gassama","authorID":"18532052","authorLastKnownAffiliationId":147273,"authorSequenceNumber":6,"affiliationSlug":"oncode-institute-A3k92","affiliationID":"146893"},{"family":"Solsona","given":"Beatriz Gomez","affiliation":"Oncode Institute","authorSlug":"beatriz-gomez-solsona-pnQzEx","authorName":"Beatriz Gomez Solsona","authorID":"4310374","authorLastKnownAffiliationId":147273,"authorSequenceNumber":7,"affiliationSlug":"oncode-institute-A3k92","affiliationID":"146893"},{"family":"Groot","given":"Marnix H. P. de","affiliation":"Oncode Institute","authorSlug":"marnix-h-p-de-groot-rgxdQO","authorName":"Marnix H. P. de Groot","authorID":"11440073","authorLastKnownAffiliationId":147273,"authorSequenceNumber":8,"affiliationSlug":"oncode-institute-A3k92","affiliationID":"146893"},{"family":"Brandsma","given":"Dieta","affiliation":"Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital","authorSlug":"dieta-brandsma-8GX8Lx","authorName":"Dieta Brandsma","authorID":"6149421","authorLastKnownAffiliationId":147273,"authorSequenceNumber":9,"affiliationSlug":"netherlands-cancer-institute-antoni-van-leeuwenhoek-r61gQ","affiliationID":"147273"},{"family":"Quail","given":"Daniela F.","affiliation":"McGill University Health Centre","authorSlug":"daniela-f-quail-EKVvj","authorName":"Daniela F. Quail","authorID":"1473261","authorLastKnownAffiliationId":22901,"authorSequenceNumber":10,"affiliationSlug":"mcgill-university-health-centre-VLEK","affiliationID":"16282"},{"family":"Walsh","given":"Logan A.","affiliation":"McGill University Health Centre","authorSlug":"logan-a-walsh-4Lbnml","authorName":"Logan A. Walsh","authorID":"5189586","authorLastKnownAffiliationId":16282,"authorSequenceNumber":11,"affiliationSlug":"mcgill-university-health-centre-VLEK","affiliationID":"16282"},{"family":"Borst","given":"Gerben R.","affiliation":"Manchester Academic Health Science Centre","authorSlug":"gerben-r-borst-vJrpk2","authorName":"Gerben R. Borst","authorID":"7086809","authorLastKnownAffiliationId":216745,"authorSequenceNumber":12,"affiliationSlug":"manchester-academic-health-science-centre-88a9","affiliationID":"16265"},{"family":"Akkari","given":"Leila","affiliation":"Oncode Institute","authorSlug":"leila-akkari-n6RPGk","authorName":"Leila Akkari","authorID":"6183533","authorLastKnownAffiliationId":147273,"authorSequenceNumber":13,"affiliationSlug":"oncode-institute-A3k92","affiliationID":"146893"}],"keywords":[],"year":2023,"shortJournal":"Nat Cancer","publisher":"Springer Science and Business Media LLC","issue":"5","volume":"4","page":"665-681","memberId":297,"issns":["2662-1347"],"editorialNotices":[],"journalSlug":"nature-cancer-4LeeR","journal":"Nature Cancer","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},"10.1080\u002F14786419.2022.2063856":{"id":11357781468,"doi":"10.1080\u002F14786419.2022.2063856","slug":"diterpenoids-profile-of-the-marine-ke5zLnkX","type":"journal-article","title":"Diterpenoids profile of the marine sponge \u003Ci\u003EChelonaplysilla erecta\u003C\u002Fi\u003E and candidacy as potential antitumor drugs investigated by molecular docking and pharmacokinetic studies","abstract":"The Chelonaplysilla genus possesses a numerous bioactive diterpenes with antiinflammatory and cytotoxic effects. The current study aimed to assess the chemical composition of C. erecta crude extract (CECE) based on its metabolomic profile that has been integrated with neural network-based virtual screening and molecular docking using liquid chromatography with high resolution mass spectrometry (LCHR-MS). In addition to the estimation of the antitumor activity of the same extract via anti-interleukin-17A (IL-17) action, along with its formulated spanlastics preparation. The CECE markedly displayed growth inhibition for HepG-2 cells at IC 50 value 16.5 ± 0.8 μg\u002FmL, whereas the spanlastic formulation revealed more eminent antitumor effect against Caco-2 cells (IC 50 = 2.8 ± 0.03 μg\u002FmL). Among the dereplicated compounds, macfarlandin F ( 16) and pourewanone ( 25) demonstrated the highest potential with co-crystallized ligand 63O within the active site of IL-17A in molecular docking studies. These findings rationalized the antitumor mechanism of marine organism for future chemotherapeutic applications.\nExperimental\nSponge materialThe marine sponge Chelonaplysilla erecta was collected by Prof. D. Hajjar and A. A. Makki, from the Red Sea, Jeddah side. The sponge possessed an upright growing skeleton with long and thick spongin fibres. Characteristically, the dendritic fibres anastomose frequently with each other in agreement with previous literature (Tsurnamal 2013). The specimens were washed then with 1% phosphate buffered saline (PBS), immediately on the boat. The specimens with their label were wrapped in aluminium foil and placed on ice, then stored at -80 °C until further processing. The specimen's surface peel was removed and immersed in xylene for 24 hours. DPX (Dibutyl Phthalate Polystyrene Xylene) was used to mount a permanent slide of the peel. Under a stereo microscope, a single fibre with its base and branches intact was extracted from the sponge for species identification. Sponge samples were identified by Prof. Dr. El-Sayd Abed El-","authors":[{"family":"Abdel‐Wahab","given":"Nada M.","affiliation":"Minia University","authorSlug":"nada-m-abdel-wahab-VKZNQR","authorName":"Nada M. Abdel‐Wahab","authorID":"11151382","authorLastKnownAffiliationId":25483,"authorSequenceNumber":1,"affiliationSlug":"minia-university-aNbb","affiliationID":"25483"},{"family":"Gomaa","given":"Alshymaa Abdel-Rahman","affiliation":"Minia University","authorSlug":"alshymaa-abdel-rahman-gomaa-vJJw6J","authorName":"Alshymaa Abdel-Rahman Gomaa","authorID":"3853697","authorLastKnownAffiliationId":25483,"authorSequenceNumber":2,"affiliationSlug":"minia-university-aNbb","affiliationID":"25483"},{"family":"Mostafa","given":"Yaser A.","affiliation":"Assiut University","authorSlug":"yaser-a-mostafa-8g4AW2","authorName":"Yaser A. Mostafa","authorID":"10087021","authorLastKnownAffiliationId":15366,"authorSequenceNumber":3,"affiliationSlug":"assiut-university-xx4w","affiliationID":"15366"},{"family":"Hajjar","given":"Dina","affiliation":"Jeddah University","authorSlug":"dina-hajjar-WGdZr1","authorName":"Dina Hajjar","authorID":"8598992","authorLastKnownAffiliationId":185067,"authorSequenceNumber":4,"affiliationSlug":"jeddah-university-JWnra","affiliationID":"185067"},{"family":"Makki","given":"Arwa A.","affiliation":"Jeddah University","authorSlug":"arwa-a-makki-M28re9","authorName":"Arwa A. Makki","authorID":"11053208","authorLastKnownAffiliationId":185067,"authorSequenceNumber":5,"affiliationSlug":"jeddah-university-JWnra","affiliationID":"185067"},{"family":"Alaaeldin","given":"Eman","affiliation":"Minia University","authorSlug":"eman-alaaeldin-d39jp1","authorName":"Eman Alaaeldin","authorID":"8081918","authorLastKnownAffiliationId":25483,"authorSequenceNumber":6,"affiliationSlug":"minia-university-aNbb","affiliationID":"25483"},{"family":"Refaat","given":"Hesham","affiliation":"Minia University","authorSlug":"hesham-refaat-LpRbOX","authorName":"Hesham Refaat","authorID":"14594740","authorLastKnownAffiliationId":6349,"authorSequenceNumber":7,"affiliationSlug":"minia-university-aNbb","affiliationID":"25483"},{"family":"Bringmann","given":"Gerhard","affiliation":"University of Würzburg","authorSlug":"gerhard-bringmann-V0XrbW","authorName":"Gerhard Bringmann","authorID":"5760182","authorLastKnownAffiliationId":17680,"authorSequenceNumber":8,"affiliationSlug":"university-of-wurzburg-l86a","affiliationID":"17680"},{"family":"Zayed","given":"Ahmed","affiliation":"Tanta University","authorSlug":"ahmed-zayed-R5Z0DD","authorName":"Ahmed Zayed","authorID":"7854126","authorLastKnownAffiliationId":1803,"authorSequenceNumber":9,"affiliationSlug":"tanta-university-abrx","affiliationID":"14783"},{"family":"Abdelmohsen","given":"Usama Ramadan","affiliation":"Minia University","authorSlug":"usama-ramadan-abdelmohsen-n6Nbe6","authorName":"Usama Ramadan Abdelmohsen","authorID":"6256977","authorLastKnownAffiliationId":25483,"authorSequenceNumber":10,"affiliationSlug":"minia-university-aNbb","affiliationID":"25483"},{"family":"Attia","given":"Eman Zekry","affiliation":"Minia University","authorSlug":"eman-zekry-attia-bWbw6","authorName":"Eman Zekry Attia","authorID":"1335015","authorLastKnownAffiliationId":25483,"authorSequenceNumber":11,"affiliationSlug":"minia-university-aNbb","affiliationID":"25483"}],"keywords":[],"year":2022,"shortJournal":"Natural Product Research","publisher":"Informa UK Limited","issue":"4","volume":"37","page":"598-602","memberId":301,"issns":["1478-6419","1478-6427"],"editorialNotices":[],"journalSlug":"natural-product-research-J1w3a","journal":"Natural Product Research","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},"10.1093\u002Fneuonc\u002Fnoac154":{"id":11569129130,"doi":"10.1093\u002Fneuonc\u002Fnoac154","slug":"clinical-significance-and-molecular-annotation-pnzQOVab","type":"journal-article","title":"Clinical significance and molecular annotation of cellular morphometric subtypes in lower-grade gliomas discovered by machine learning","abstract":"BACKGROUND\n Lower grade gliomas (LGG) are heterogenous diseases by clinical, histological, and molecular criteria. We aimed to personalize the diagnosis and therapy of LGG patients by developing and validating robust cellular morphometric subtypes (CMS) and to uncover the molecular signatures underlying these subtypes.\n \n \n METHODS\n Cellular morphometric biomarkers (CMBs) were identified with artificial intelligence technique from TCGA-LGG cohort. Consensus clustering was used to define CMS. Survival analysis was performed to assess the clinical impact of CMBs and CMS. A nomogram was constructed to predict 3- and 5- year overall survival (OS) of LGG patients. Tumor mutational burden (TMB), and immune cell infiltration between subtypes were analyzed using the Mann-Whitney test. The double-blinded validation for important immunotherapy-related biomarkers were executed using immunohistochemistry (IHC).\n \n \n RESULTS\n We developed a machine learning pipeline to extract CMBs from whole slide images of tissue histology; identifying and externally validating robust CMS of LGGs in multi-center cohorts. The subtypes had independent predicted OS across all three independent cohorts. In the TCGA-LGG cohort, patients within the poor-prognosis subtype responded poorly to primary and follow-up therapies. LGGs within the poor-prognosis subtype were characterized by high mutational burden, high frequencies of copy number alterations, and high levels of tumor-infiltrating lymphocytes and immune checkpoint genes. Higher levels of PD-1\u002FPD-L1\u002FCTLA-4 were confirmed by immunohistochemical staining. In addition, the subtypes learned from LGG demonstrates translational impact on glioblastoma (GBM).\n \n \n CONCLUSIONS\n We developed and validated a framework (CMS-ML) for CMS discovery in LGG associated with specific molecular alterations, immune micro-environment, prognosis, and treatment response.","authors":[{"family":"Li","given":"Xiaoping","affiliation":"Lawrence Berkeley National Laboratory","authorSlug":"xiaoping-li-YZdJPz","authorName":"Xiaoping Li","authorID":"4801807","authorLastKnownAffiliationId":5150,"authorSequenceNumber":1,"affiliationSlug":"lawrence-berkeley-national-laboratory-AOJe","affiliationID":"10149"},{"family":"Jin","given":"Xiaoqing","affiliation":"Lawrence Berkeley National Laboratory","authorSlug":"xiaoqing-jin-V26MZ","authorName":"Xiaoqing Jin","authorID":"1316082","authorLastKnownAffiliationId":136933,"authorSequenceNumber":2,"affiliationSlug":"lawrence-berkeley-national-laboratory-AOJe","affiliationID":"10149"},{"family":"Ahmadian","given":"Saman S.","affiliation":"Stanford University","authorSlug":"saman-s-ahmadian-1gxP8j","authorName":"Saman S. Ahmadian","authorID":"8753903","authorLastKnownAffiliationId":185823,"authorSequenceNumber":3,"affiliationSlug":"stanford-university-EVVW","affiliationID":"23761"},{"family":"Yang","given":"Xu","affiliation":"Lawrence Berkeley National Laboratory","authorSlug":"xu-yang-lZvwpk","authorName":"Xu Yang","authorID":"7205380","authorLastKnownAffiliationId":136933,"authorSequenceNumber":4,"affiliationSlug":"lawrence-berkeley-national-laboratory-AOJe","affiliationID":"10149"},{"family":"Tian","given":"Sufang","affiliation":"Zhongnan Hospital of Wuhan University","authorSlug":"sufang-tian-G3WgZb","authorName":"Sufang Tian","authorID":"6766757","authorLastKnownAffiliationId":136933,"authorSequenceNumber":5,"affiliationSlug":"zhongnan-hospital-of-wuhan-university-n6WZD","affiliationID":"136933"},{"family":"Cai","given":"Yuxiang","affiliation":"Zhongnan Hospital of Wuhan University","authorSlug":"yuxiang-cai-M23yrp","authorName":"Yuxiang Cai","authorID":"8448252","authorLastKnownAffiliationId":1317,"authorSequenceNumber":6,"affiliationSlug":"zhongnan-hospital-of-wuhan-university-n6WZD","affiliationID":"136933"},{"family":"Chawla","given":"Kuldeep","affiliation":"Lawrence Berkeley National Laboratory","authorSlug":"kuldeep-chawla-gZbgQK","authorName":"Kuldeep Chawla","authorID":"3824414","authorLastKnownAffiliationId":10149,"authorSequenceNumber":7,"affiliationSlug":"lawrence-berkeley-national-laboratory-AOJe","affiliationID":"10149"},{"family":"Snijders","given":"Antoine M.","affiliation":"Lawrence Berkeley National Laboratory","authorSlug":"antoine-m-snijders-zRElNY","authorName":"Antoine M. Snijders","authorID":"5353994","authorLastKnownAffiliationId":10149,"authorSequenceNumber":8,"affiliationSlug":"lawrence-berkeley-national-laboratory-AOJe","affiliationID":"10149"},{"family":"Xia","given":"Yankai","affiliation":"Nanjing Medical University","authorSlug":"yankai-xia-OV2wJj","authorName":"Yankai Xia","authorID":"5079934","authorLastKnownAffiliationId":13502,"authorSequenceNumber":9,"affiliationSlug":"nanjing-medical-university-9N92","affiliationID":"13502"},{"family":"Diest","given":"Paul J. van","affiliation":"University Medical Center Utrecht","authorSlug":"paul-j-van-diest-0GMnVy","authorName":"Paul J. van Diest","authorID":"4936212","authorLastKnownAffiliationId":988,"authorSequenceNumber":10,"affiliationSlug":"university-medical-center-utrecht-3kd","affiliationID":"988"},{"family":"Weiss","given":"William A.","affiliation":"Neurological Surgery","authorSlug":"william-a-weiss-pnP1JN","authorName":"William A. Weiss","authorID":"6524130","authorLastKnownAffiliationId":260283,"authorSequenceNumber":11,"affiliationSlug":"neurological-surgery-WxxE5","affiliationID":"261604"},{"family":"Mao","given":"Jian‐Hua","affiliation":"Lawrence Berkeley National Laboratory","authorSlug":"jian-hua-mao-keEYZE","authorName":"Jian‐Hua Mao","authorID":"5120824","authorLastKnownAffiliationId":10149,"authorSequenceNumber":12,"affiliationSlug":"lawrence-berkeley-national-laboratory-AOJe","affiliationID":"10149"},{"family":"Li","given":"Zhiqiang","affiliation":"Zhongnan Hospital of Wuhan University","authorSlug":"zhiqiang-li-KJjv5","authorName":"Zhiqiang Li","authorID":"937635","authorLastKnownAffiliationId":258053,"authorSequenceNumber":13,"affiliationSlug":"zhongnan-hospital-of-wuhan-university-n6WZD","affiliationID":"136933"},{"family":"Vogel","given":"Hannes","affiliation":"Stanford University","authorSlug":"hannes-vogel-MV9grX","authorName":"Hannes Vogel","authorID":"4845352","authorLastKnownAffiliationId":23761,"authorSequenceNumber":14,"affiliationSlug":"stanford-university-EVVW","affiliationID":"23761"},{"family":"Chang","given":"Hang","affiliation":"Lawrence Berkeley National Laboratory","authorSlug":"hang-chang-aXgpN9","authorName":"Hang Chang","authorID":"6286783","authorLastKnownAffiliationId":148603,"authorSequenceNumber":15,"affiliationSlug":"lawrence-berkeley-national-laboratory-AOJe","affiliationID":"10149"}],"year":2022,"publisher":"Oxford University Press (OUP)","issue":"1","volume":"25","page":"68-81","memberId":286,"issns":["1522-8517","1523-5866"],"editorialNotices":[],"journalSlug":"neuro-oncology-0GvYZ","journal":"Neuro-Oncology","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},"10.4172\u002F2325-9701.s1-004":{"id":130144580,"doi":"10.4172\u002F2325-9701.s1-004","slug":"role-of-il-17-in-glioma-lpAzGE","type":"journal-article","title":"Role of IL-17 in Glioma Progression","abstract":"There is increasing evidence in the literature pointing to an important role of inflammation during initiation and progression of cancer. Glioblastoma is the most common malignant primary brain tumor with approximately 23,000 newly-diagnosed cases each year in the United States, and has a dismal median survival of only 15 months. Although the blood-brain barrier maintains an immune-privileged status of the brain under steady state, intracranial tumors including gliomas are invariably infiltrated with various types of immune cells. The T helper 17 (Th17) cells, a recently discovered interleukin (IL)-17-producing T cell subtype, have been reported in several extracranial and some intracranial tumors, where they have been implicated in either pro- or antitumor activity depending on the tumor type. Here, we present a succinct review of the current literature on the prevalence and potential role of IL-17 in malignant gliomas. Further mechanistic studies on IL-17 mediated inflammatory pathway in gliomas may provide with opportunities for novel immunotherapeutic interventions.","authors":[{"family":"Parajuli","given":"Prahlad","affiliation":"Karmanos Cancer Institute","authorSlug":"prahlad-parajuli-5Gl4gV","authorName":"Prahlad Parajuli","authorID":"5474125","authorLastKnownAffiliationId":11741,"authorSequenceNumber":1,"affiliationSlug":"karmanos-cancer-institute-G5z6L","affiliationID":"170613"},{"family":"Mittal","given":"Sandeep","affiliation":"Karmanos Cancer Institute","authorSlug":"sandeep-mittal-8GXGxY","authorName":"Sandeep Mittal","authorID":"6136321","authorLastKnownAffiliationId":140389,"authorSequenceNumber":2,"affiliationSlug":"karmanos-cancer-institute-G5z6L","affiliationID":"170613"}],"keywords":["Article"],"year":2013,"shortJournal":"J Spine Neurosurg","publisher":"OMICS Publishing Group","retracted":false,"memberId":2674,"issns":["2325-9701"],"editorialNotices":[],"journalSlug":"journal-of-spine-neurosurgery-ZGp0p","journal":"Journal of Spine &Amp; Neurosurgery","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]}},"tallies":{"10.4172\u002F2325-9701.s1-004":{"total":23,"supporting":1,"contradicting":0,"mentioning":22,"unclassified":0,"doi":"10.4172\u002F2325-9701.s1-004","citingPublications":19}},"selectCitation":null,"references":[],"referencesTotalCount":76,"referencePapers":{},"referenceTallies":{},"referencesByPapers":[],"paperLoadTracker":{"state":"loaded","key":"role-of-il-17-in-glioma-lpAzGE"},"citingCountsLoadTracker":{"state":"loading"},"citationsLoadTracker":{"state":"loaded"},"referencesLoadTracker":{"state":"loaded"},"claimPaperLoadTracker":{},"flagCitationLoadTracker":{},"filters":{"showMobile":false,"sort":{"id":"relevancy","value":null,"label":"Relevance"},"supporting":null,"mentioning":null,"contradicting":null,"unclassified":null,"selfCite":null,"independent":null,"publishedRange":null,"citationsPerPage":10,"currentPage":1,"textMatch":"","citationIDs":[],"sourceDOIIDs":[],"withCitationStatements":true,"withoutCitationStatements":true,"journals":[],"authors":[],"pubtypes":[],"sections":[],"showReferences":false},"flag":{"citation":null,"citationType":null,"type":"","comment":""},"moreLikeThisResults":null,"moreLikeThisLoading":false,"exportReportLoading":false},"loginModal":{"mode":"login","name":{"placeholder":"Full Name","type":"text","value":""},"email":{"type":"email","placeholder":"Email","value":""},"password":{"type":"password","placeholder":"Password","value":""},"repeatPassword":{"type":"password","placeholder":"Repeat Password","value":""},"privacyAgreed":false,"loading":false,"userSignupType":null,"userSignupTypeLoading":false,"userSignupTypeEmail":null,"userSignupTypeOrg":null,"userSignupTypeEmailDomains":null,"fetchedSignupType":false,"fetchedSignupTypeError":false}}</script><script id="__LOADABLE_REQUIRED_CHUNKS__" type="application/json">[]</script><script id="__LOADABLE_REQUIRED_CHUNKS___ext" type="application/json">{"namedChunks":[]}</script><script async="" data-chunk="main" src="https://cdn.scite.ai/assets/dist/main.33b6f5c40898cc5cded7.js"></script><div><script id="profitwell-js" data-pw-auth="eba7f4438ac9b91fc798c9620e35aa80"> (function(i,s,o,g,r,a,m){i[o]=i[o]||function(){(i[o].q=i[o].q||[]).push(arguments)}; a=s.createElement(g);m=s.getElementsByTagName(g)[0];a.async=1;a.src=r+'?auth='+ s.getElementById(o+'-js').getAttribute('data-pw-auth');m.parentNode.insertBefore(a,m); })(window,document,'profitwell','script','https://public.profitwell.com/js/profitwell.js'); </script><!-- Global site tag (gtag.js) - Google Ads: 614125746 --> <script async src="https://www.googletagmanager.com/gtag/js?id=AW-614125746"></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag("consent", "default", {ad_storage: "denied", analytics_storage: "denied", wait_for_update: 1500}); gtag('js', new Date()); gtag('config', 'AW-614125746'); </script> <script src="https://www.dwin1.com/19038.js" type="text/javascript" defer="defer"></script> <script src="https://script.tapfiliate.com/tapfiliate.js" type="text/javascript" async></script> <script type="text/javascript"> (function(t,a,p){t.TapfiliateObject=a;t[a]=t[a]||function(){ (t[a].q=t[a].q||[]).push(arguments)}})(window,'tap'); tap('create', '48731-1a14bc', { integration: "javascript" }); tap('detect'); </script> <script src="https://fast.wistia.com/embed/medias/o5vno207sz.jsonp" async></script> <script src="https://fast.wistia.com/assets/external/E-v1.js" async></script> <!-- MathJax --> <script> window.__MathJax_State__ = { isReady: false, promise: new Promise(resolve => { window.MathJax = { // MathJax can be configured as desired in addition to these options. startup: { ready: () => { // Do whatever MathJax would normally do at this point. MathJax.startup.defaultReady(); // Set the flag and resolve the promise. window.__MathJax_State__.isReady = true; resolve(); } }, tex: { inlineMath: [ ["$", "$"], ], }, svg: { fontCache: "global" } }; }) }; </script> <script> var _rollbarConfig = { accessToken: "2c3f1a7fb80c4667a8370b6d5e60b850", captureUncaught: true, captureUnhandledRejections: true, payload: { environment: "production", client: { javascript: { code_version: "null" } } } }; // Rollbar Snippet !function(r){function e(n){if(o[n])return o[n].exports;var t=o[n]={exports:{},id:n,loaded:!1};return r[n].call(t.exports,t,t.exports,e),t.loaded=!0,t.exports}var o={};return e.m=r,e.c=o,e.p="",e(0)}([function(r,e,o){"use strict";var n=o(1),t=o(4);_rollbarConfig=_rollbarConfig||{},_rollbarConfig.rollbarJsUrl=_rollbarConfig.rollbarJsUrl||"https://cdnjs.cloudflare.com/ajax/libs/rollbar.js/2.24.0/rollbar.min.js",_rollbarConfig.async=void 0===_rollbarConfig.async||_rollbarConfig.async;var a=n.setupShim(window,_rollbarConfig),l=t(_rollbarConfig);window.rollbar=n.Rollbar,a.loadFull(window,document,!_rollbarConfig.async,_rollbarConfig,l)},function(r,e,o){"use strict";function n(r){return function(){try{return r.apply(this,arguments)}catch(r){try{console.error("[Rollbar]: Internal error",r)}catch(r){}}}}function t(r,e){this.options=r,this._rollbarOldOnError=null;var o=s++;this.shimId=function(){return o},"undefined"!=typeof window&&window._rollbarShims&&(window._rollbarShims[o]={handler:e,messages:[]})}function a(r,e){if(r){var o=e.globalAlias||"Rollbar";if("object"==typeof r[o])return r[o];r._rollbarShims={},r._rollbarWrappedError=null;var t=new p(e);return n(function(){e.captureUncaught&&(t._rollbarOldOnError=r.onerror,i.captureUncaughtExceptions(r,t,!0),i.wrapGlobals(r,t,!0)),e.captureUnhandledRejections&&i.captureUnhandledRejections(r,t,!0);var n=e.autoInstrument;return e.enabled!==!1&&(void 0===n||n===!0||"object"==typeof n&&n.network)&&r.addEventListener&&(r.addEventListener("load",t.captureLoad.bind(t)),r.addEventListener("DOMContentLoaded",t.captureDomContentLoaded.bind(t))),r[o]=t,t})()}}function l(r){return n(function(){var e=this,o=Array.prototype.slice.call(arguments,0),n={shim:e,method:r,args:o,ts:new Date};window._rollbarShims[this.shimId()].messages.push(n)})}var i=o(2),s=0,d=o(3),c=function(r,e){return new t(r,e)},p=d.bind(null,c);t.prototype.loadFull=function(r,e,o,t,a){var l=function(){var e;if(void 0===r._rollbarDidLoad){e=new Error("rollbar.js did not load");for(var o,n,t,l,i=0;o=r._rollbarShims[i++];)for(o=o.messages||[];n=o.shift();)for(t=n.args||[],i=0;i<t.length;++i)if(l=t[i],"function"==typeof l){l(e);break}}"function"==typeof a&&a(e)},i=!1,s=e.createElement("script"),d=e.getElementsByTagName("script")[0],c=d.parentNode;s.crossOrigin="",s.src=t.rollbarJsUrl,o||(s.async=!0),s.onload=s.onreadystatechange=n(function(){if(!(i||this.readyState&&"loaded"!==this.readyState&&"complete"!==this.readyState)){s.onload=s.onreadystatechange=null;try{c.removeChild(s)}catch(r){}i=!0,l()}}),c.insertBefore(s,d)},t.prototype.wrap=function(r,e,o){try{var n;if(n="function"==typeof e?e:function(){return e||{}},"function"!=typeof r)return r;if(r._isWrap)return r;if(!r._rollbar_wrapped&&(r._rollbar_wrapped=function(){o&&"function"==typeof o&&o.apply(this,arguments);try{return r.apply(this,arguments)}catch(o){var e=o;throw e&&("string"==typeof e&&(e=new String(e)),e._rollbarContext=n()||{},e._rollbarContext._wrappedSource=r.toString(),window._rollbarWrappedError=e),e}},r._rollbar_wrapped._isWrap=!0,r.hasOwnProperty))for(var t in r)r.hasOwnProperty(t)&&(r._rollbar_wrapped[t]=r[t]);return r._rollbar_wrapped}catch(e){return r}};for(var u="log,debug,info,warn,warning,error,critical,global,configure,handleUncaughtException,handleUnhandledRejection,captureEvent,captureDomContentLoaded,captureLoad".split(","),f=0;f<u.length;++f)t.prototype[u[f]]=l(u[f]);r.exports={setupShim:a,Rollbar:p}},function(r,e){"use strict";function o(r,e,o){if(r){var t;"function"==typeof e._rollbarOldOnError?t=e._rollbarOldOnError:r.onerror&&!r.onerror.belongsToShim&&(t=r.onerror,e._rollbarOldOnError=t);var a=function(){var o=Array.prototype.slice.call(arguments,0);n(r,e,t,o)};a.belongsToShim=o,r.onerror=a}}function n(r,e,o,n){r._rollbarWrappedError&&(n[4]||(n[4]=r._rollbarWrappedError),n[5]||(n[5]=r._rollbarWrappedError._rollbarContext),r._rollbarWrappedError=null),e.handleUncaughtException.apply(e,n),o&&o.apply(r,n)}function t(r,e,o){if(r){"function"==typeof r._rollbarURH&&r._rollbarURH.belongsToShim&&r.removeEventListener("unhandledrejection",r._rollbarURH);var n=function(r){var o,n,t;try{o=r.reason}catch(r){o=void 0}try{n=r.promise}catch(r){n="[unhandledrejection] error getting `promise` from event"}try{t=r.detail,!o&&t&&(o=t.reason,n=t.promise)}catch(r){t="[unhandledrejection] error getting `detail` from event"}o||(o="[unhandledrejection] error getting `reason` from event"),e&&e.handleUnhandledRejection&&e.handleUnhandledRejection(o,n)};n.belongsToShim=o,r._rollbarURH=n,r.addEventListener("unhandledrejection",n)}}function a(r,e,o){if(r){var n,t,a="EventTarget,Window,Node,ApplicationCache,AudioTrackList,ChannelMergerNode,CryptoOperation,EventSource,FileReader,HTMLUnknownElement,IDBDatabase,IDBRequest,IDBTransaction,KeyOperation,MediaController,MessagePort,ModalWindow,Notification,SVGElementInstance,Screen,TextTrack,TextTrackCue,TextTrackList,WebSocket,WebSocketWorker,Worker,XMLHttpRequest,XMLHttpRequestEventTarget,XMLHttpRequestUpload".split(",");for(n=0;n<a.length;++n)t=a[n],r[t]&&r[t].prototype&&l(e,r[t].prototype,o)}}function l(r,e,o){if(e.hasOwnProperty&&e.hasOwnProperty("addEventListener")){for(var n=e.addEventListener;n._rollbarOldAdd&&n.belongsToShim;)n=n._rollbarOldAdd;var t=function(e,o,t){n.call(this,e,r.wrap(o),t)};t._rollbarOldAdd=n,t.belongsToShim=o,e.addEventListener=t;for(var a=e.removeEventListener;a._rollbarOldRemove&&a.belongsToShim;)a=a._rollbarOldRemove;var l=function(r,e,o){a.call(this,r,e&&e._rollbar_wrapped||e,o)};l._rollbarOldRemove=a,l.belongsToShim=o,e.removeEventListener=l}}r.exports={captureUncaughtExceptions:o,captureUnhandledRejections:t,wrapGlobals:a}},function(r,e){"use strict";function o(r,e){this.impl=r(e,this),this.options=e,n(o.prototype)}function n(r){for(var e=function(r){return function(){var e=Array.prototype.slice.call(arguments,0);if(this.impl[r])return this.impl[r].apply(this.impl,e)}},o="log,debug,info,warn,warning,error,critical,global,configure,handleUncaughtException,handleUnhandledRejection,_createItem,wrap,loadFull,shimId,captureEvent,captureDomContentLoaded,captureLoad".split(","),n=0;n<o.length;n++)r[o[n]]=e(o[n])}o.prototype._swapAndProcessMessages=function(r,e){this.impl=r(this.options);for(var o,n,t;o=e.shift();)n=o.method,t=o.args,this[n]&&"function"==typeof this[n]&&("captureDomContentLoaded"===n||"captureLoad"===n?this[n].apply(this,[t[0],o.ts]):this[n].apply(this,t));return this},r.exports=o},function(r,e){"use strict";r.exports=function(r){return function(e){if(!e&&!window._rollbarInitialized){r=r||{};for(var o,n,t=r.globalAlias||"Rollbar",a=window.rollbar,l=function(r){return new a(r)},i=0;o=window._rollbarShims[i++];)n||(n=o.handler),o.handler._swapAndProcessMessages(l,o.messages);window[t]=n,window._rollbarInitialized=!0}}}}]); // End Rollbar Snippet </script> <script> (function(w,d,t,r,u) { var f,n,i; w[u]=w[u]||[],f=function() { var o={ti:"343050743", enableAutoSpaTracking: true}; o.q=w[u],w[u]=new UET(o),w[u].push("pageLoad") }, n=d.createElement(t),n.src=r,n.async=1,n.onload=n.onreadystatechange=function() { var s=this.readyState; s&&s!=="loaded"&&s!=="complete"||(f(),n.onload=n.onreadystatechange=null) }, i=d.getElementsByTagName(t)[0],i.parentNode.insertBefore(n,i) }) (window,document,"script","//bat.bing.com/bat.js","uetq"); </script> <script> !function(f,b,e,v,n,t,s) {if(f.fbq)return;n=f.fbq=function(){n.callMethod? n.callMethod.apply(n,arguments):n.queue.push(arguments)}; if(!f._fbq)f._fbq=n;n.push=n;n.loaded=!0;n.version='2.0'; n.queue=[];t=b.createElement(e);t.async=!0; t.src=v;s=b.getElementsByTagName(e)[0]; s.parentNode.insertBefore(t,s)}(window, document,'script', 'https://connect.facebook.net/en_US/fbevents.js'); fbq('init', '927411631440706'); fbq('track', 'PageView'); </script> <noscript><img height="1" width="1" style="display:none" src="https://www.facebook.com/tr?id=927411631440706&ev=PageView&noscript=1" /></noscript> <script> !function(){ if (!window.churnkey || !window.churnkey.created) { window.churnkey = { created: true }; const a = document.createElement('script'); a.src = 'https://assets.churnkey.co/js/app.js?appId=2l1x8e2dl'; a.async = true; const b = document.getElementsByTagName('script')[0]; b.parentNode.insertBefore(a, b); } }(); </script> <script src='https://js.chilipiper.com/marketing.js' type='text/javascript' /> <script src="https://tag.clearbitscripts.com/v1/pk_fc279c8e6fe02304f4b6e672bc239206/tags.js" referrerpolicy="strict-origin-when-cross-origin"></script> </div></body>