Discovery points to new cancer immunotherapy option

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LifeFlight began using the larger twin engine BK-117 craft, which is capable of simultaneous transport of two patients, in 1986. (photo by John Howser) </p> " data-medium-file="https://vumc-reporter.s3.amazonaws.com/uploads/SEE-F.P.O_7-450x291.jpg" data-large-file="https://vumc-reporter.s3.amazonaws.com/uploads/SEE-F.P.O_7-790x512.jpg" /> <h6 class="featured-story__category">Emergency & Trauma</h6> <h3 class="featured-story__title">The LifeFlight legacy: 40 years in 40 photos</h3> </a> </div> </div> </div> </header> <main id="primary" class="site-main"> <header class="single-post-header"> <div class="single-post-header__eyebrow"> <a href="https://news.vumc.org/section/cancer/" class="single-post-header__category"> Cancer </a> <h3 class="single-post-header__date"> February 21, 2019 </h3> </div> <h1>Discovery points to new cancer immunotherapy option</h1> <div class="single-post-header__excerpt"> <p>An international team involving Vanderbilt researchers has discovered that a new “checkpoint” protein on immune system cells is active in tumors, and that blocking it — in combination with other treatments — is a successful therapeutic approach in mouse models of cancer. </p> </div> </header> <div class="content-with-sidebar"> <article id="post-282862" class="post-282862 post type-post status-publish format-standard has-post-thumbnail hentry category-cancer tag-cell-journal tag-department-of-otolaryngology-head-and-neck-surgery tag-immunology tag-immunotherapy vumc_highlight-research old_category-reporter old_tag-amy-and-barry-baker-lab old_tag-cancer-immunotherapy old_tag-cancer-research old_tag-cell old_tag-checkpoint-inhibitors old_tag-department-of-otolaryngology old_tag-featured-reporter old_tag-flow-cytometry-shared-resource old_tag-immune-system old_tag-immunotherapy old_tag-nci old_tag-nih old_tag-nih-funding old_tag-reporter-feb-22-2019 old_tag-t-cell old_tag-vanderbilt-ingram-cancer-center old_tag-vanderbilt-institute-for-infection-immunology-and-inflammation old_tag-young-kim"> <div class="post-opening"> <div class="post-opening__share-print share-print"> <div class="share-print__share"> <h5>Share:</h5> <a href="https://www.facebook.com/sharer/sharer.php?u=https%3A%2F%2Fnews.vumc.org%2F2019%2F02%2F21%2Fdiscovery-cancer-immunotherapy%2F" target="_blank" rel="noopener noreferrer" class="share-link share-link--facebook"> <span class="screen-reader-text">Share on Facebook</span> <img src="https://news.vumc.org/wp-content/themes/vumc-news/images/social/facebook_blue.png" alt="Facebook" /> </a> <a href="https://bsky.app/intent/compose/?text=Discovery+points+to+new+cancer+immunotherapy+option https%3A%2F%2Fnews.vumc.org%2F2019%2F02%2F21%2Fdiscovery-cancer-immunotherapy%2F" target="_blank" rel="noopener noreferrer" class="share-link share-link--bsky"> <span class="screen-reader-text">Share on Bsky</span> <img src="https://news.vumc.org/wp-content/themes/vumc-news/images/social/bluesky_blue.png" alt="Bluesky" /> </a> <a 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href="mailto:?subject=Discovery+points+to+new+cancer+immunotherapy+option&body=https%3A%2F%2Fnews.vumc.org%2F2019%2F02%2F21%2Fdiscovery-cancer-immunotherapy%2F" target="_blank" rel="noopener noreferrer" class="share-link share-link--email"> <span class="screen-reader-text">Share via Email</span> <img src="https://news.vumc.org/wp-content/themes/vumc-news/images/social/email_blue.png" alt="Email" /> </a> </div> <div class="share-print__print"> <h5>Print:</h5> <a href="javascript:window.print()" class="post-opening__print-link"> <span class="screen-reader-text">Print this article</span> <img src="https://news.vumc.org/wp-content/themes/vumc-news/images/social/print_blue.png" alt="Print" /> </a> </div> </div> <div class="post-opening__byline"> By: Leigh MacMillan </div> </div> <div class="entry-content clearfix"> <figure id="attachment_282863" aria-describedby="caption-attachment-282863" style="width: 685px" class="wp-caption aligncenter"><img decoding="async" data-attachment-id="282863" data-permalink="https://news.vumc.org/2019/02/21/discovery-cancer-immunotherapy/kim-and-korrer-lab-ar0181/" data-orig-file="https://vumc-reporter.s3.amazonaws.com/uploads/Kim-and-Korrer-lab-AR0181.jpg" data-orig-size="685,367" data-comments-opened="0" data-image-meta="{"aperture":"6.3","credit":"","camera":"Canon EOS 5D Mark IV","caption":"Young Kim, M.D., Ph.D., and Michael Korrer, Ph.D.\rRecent publication in the journal Cell describing a new way to enhance immune system killing of tumors.\rVanderbilt University Medical Center\r\rPhoto: Anne Rayner; VU","created_timestamp":"1547135741","copyright":"","focal_length":"24","iso":"1250","shutter_speed":"0.0125","title":"","orientation":"1"}" data-image-title="Kim and Korrer lab AR0181" data-image-description="" data-image-caption="<p>Young Kim, MD, PhD, left, Michael Korrer, PhD, and colleagues are studying a potential new cancer immunotherapy option. (photo by Anne Rayner)</p> " data-medium-file="https://vumc-reporter.s3.amazonaws.com/uploads/Kim-and-Korrer-lab-AR0181-450x241.jpg" data-large-file="https://vumc-reporter.s3.amazonaws.com/uploads/Kim-and-Korrer-lab-AR0181.jpg" class="size-full wp-image-282863" src="https://vumc-reporter.s3.amazonaws.com/uploads/Kim-and-Korrer-lab-AR0181.jpg" alt="Young Kim, MD, PhD, left, Michael Korrer, PhD, and colleagues are studying a potential new cancer immunotherapy option." width="685" height="367" srcset="https://vumc-reporter.s3.amazonaws.com/uploads/Kim-and-Korrer-lab-AR0181.jpg 685w, https://vumc-reporter.s3.amazonaws.com/uploads/Kim-and-Korrer-lab-AR0181-450x241.jpg 450w, https://vumc-reporter.s3.amazonaws.com/uploads/Kim-and-Korrer-lab-AR0181-185x100.jpg 185w" sizes="(max-width: 685px) 100vw, 685px" /><figcaption id="caption-attachment-282863" class="wp-caption-text">Young J. Kim, MD, PhD, left, Michael Korrer, PhD, and colleagues are studying a potential new cancer immunotherapy option. (photo by Anne Rayner)</figcaption></figure> <p>An international team involving Vanderbilt researchers has discovered that a new “checkpoint” protein on immune system cells is active in tumors, and that blocking it — in combination with other treatments — is a successful therapeutic approach in mouse models of cancer. The findings were reported in the journal <a href="https://www.cell.com/cell/fulltext/S0092-8674(18)31381-3" target="_blank" rel="noopener"><em>Cell</em></a>.</p> <p>Checkpoint proteins are regulators of the immune response; they put on the “brakes” to protect normal tissues. Checkpoint inhibitor immunotherapies take these brakes off, unleashing the immune system’s cancer-killing power. They have been remarkably effective against a number of cancers.</p> <p>Currently available checkpoint inhibitors target one of two immune system checkpoint pathways, but many more checkpoint proteins exist, said Michael Korrer, PhD, a postdoctoral fellow working with <a href="https://ww2.mc.vanderbilt.edu/bakerlab/53644" target="_blank" rel="noopener">Young J. Kim</a>, MD, PhD, Barry and Amy Baker Professor of Laryngeal, Head and Neck Research at Vanderbilt.</p> <p>Korrer and Kim were exploring the molecular landscape of immune system cells in human head and neck cancers removed during surgery. They were particularly interested in natural killer (NK) cells, innate immune cells that detect and kill cells infected by viruses and cancer cells.</p> <p>“We were characterizing natural killer cells in head and neck tumor samples, looking for cell surface proteins that might explain why the NK cells aren’t working as well as they should be,” Korrer said.</p> <p>The researchers used the <a href="https://ww2.mc.vanderbilt.edu/flowcytometry/" target="_blank" rel="noopener">Vanderbilt Flow Cytometry Shared Resource</a> to sort and characterize immune cells based on surface proteins.</p> <p>They found that a protein called NKG2A was the only inhibitory receptor with increased expression on NK cells in the head and neck tumors. But NKG2A is also expressed by NK cells circulating in the blood, and it only had slightly higher expression in the tumors, Korrer said.</p> <p>When they looked at proteins on cytotoxic (CD8-expressing) T cells, however, Korrer noticed a jump in NKG2A.</p> <p>“We weren’t expecting that, since NKG2A is normally associated with NK cells,” he said. “But it was clearly being expressed by CD8 T cells in the head and neck tumor samples and not in the blood. That caught our attention.”</p> <p>Cytotoxic T cells also kill virus-infected and cancer cells, but they must first be activated by recognizing a specific antigen.</p> <p>In further studies, Korrer confirmed that the tumor cells expressed the protein that interacts with NKG2A, called HLA-E, and that NKG2A inhibited cytotoxic T cell activity in the tumors. Expression of NKG2A in the head and neck tumors was associated with worse clinical outcome.</p> <p>Korrer and Kim then connected with Thorbald van Hall, PhD, and his colleagues at Leiden University Medical Center in the Netherlands, who had extensively studied HLA-E, and with Innate Pharma, a company in Marseille, France that has developed an anti-NKG2A antibody therapy called monalizumab.</p> <p>Using mouse tumor models, the researchers found that blocking NKG2A with monalizumab alone had minimal therapeutic effect. However, combining monalizumab with a cancer vaccine designed to stimulate an anti-tumor immune response reduced tumor growth and increased progression-free survival time.</p> <p>“It appears that NKG2A-targeted treatments have to be combined with something causing inflammation in the tumor, such as a cancer vaccine,” Korrer said.</p> <p>The researchers demonstrated that the vaccine stimulated the expression of HLA-E in the tumor, suggesting that tumors engage the NKG2A pathway as a mechanism for adaptive resistance to vaccine therapy — and that blocking the pathway may improve responses to cancer vaccines.</p> <p>In a separate study, researchers at Innate Pharma reported interim results from a Phase II clinical trial of monalizumab combined with cetuximab, an antibody against the EGF receptor, in patients with previously treated head and neck cancer. They found that 30 percent of the patients had a reduced tumor burden in response to the combined treatment.</p> <p>“Right now, NKG2A looks like it might be the third most successful immunotherapy checkpoint, which is really exciting,” Korrer said.</p> <p>Korrer and Kim are using cellular and animal models to further explore the mechanism of action for combined cetuximab and monalizumab, the immune system cells that are active, and how cancer vaccines promote HLA-E expression in tumor cells.</p> <p>This research was supported by the National Institutes of Health (grant CA178613), the <a href="https://ww2.mc.vanderbilt.edu/bakerlab/" target="_blank" rel="noopener">Amy and Barry Baker Lab</a>, the Dutch Cancer Society and Innate Pharma.</p> <div id='jp-relatedposts' class='jp-relatedposts' > <h3 class="jp-relatedposts-headline"><em>Related</em></h3> </div> </div> <div class="share-bar share-print"> <div class="share-print__share"> <h5>Share:</h5> <a 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<span class="pojo-a11y-toolbar-icon"><svg version="1.1" xmlns="http://www.w3.org/2000/svg" width="1em" viewBox="0 0 448 448"><title>Negative Contrast</title><path fill="currentColor" d="M416 240c-23.75-36.75-56.25-68.25-95.25-88.25 10 17 15.25 36.5 15.25 56.25 0 61.75-50.25 112-112 112s-112-50.25-112-112c0-19.75 5.25-39.25 15.25-56.25-39 20-71.5 51.5-95.25 88.25 42.75 66 111.75 112 192 112s149.25-46 192-112zM236 144c0-6.5-5.5-12-12-12-41.75 0-76 34.25-76 76 0 6.5 5.5 12 12 12s12-5.5 12-12c0-28.5 23.5-52 52-52 6.5 0 12-5.5 12-12zM448 240c0 6.25-2 12-5 17.25-46 75.75-130.25 126.75-219 126.75s-173-51.25-219-126.75c-3-5.25-5-11-5-17.25s2-12 5-17.25c46-75.5 130.25-126.75 219-126.75s173 51.25 219 126.75c3 5.25 5 11 5 17.25z"></path></svg></span><span class="pojo-a11y-toolbar-text">Negative Contrast</span> </a> </li> <li class="pojo-a11y-toolbar-item"> <a href="#" class="pojo-a11y-toolbar-link pojo-a11y-btn-background-group pojo-a11y-btn-light-background" data-action="light-background" data-action-group="schema" tabindex="-1" role="button"> <span class="pojo-a11y-toolbar-icon"><svg version="1.1" xmlns="http://www.w3.org/2000/svg" width="1em" viewBox="0 0 448 448"><title>Light Background</title><path fill="currentColor" d="M184 144c0 4.25-3.75 8-8 8s-8-3.75-8-8c0-17.25-26.75-24-40-24-4.25 0-8-3.75-8-8s3.75-8 8-8c23.25 0 56 12.25 56 40zM224 144c0-50-50.75-80-96-80s-96 30-96 80c0 16 6.5 32.75 17 45 4.75 5.5 10.25 10.75 15.25 16.5 17.75 21.25 32.75 46.25 35.25 74.5h57c2.5-28.25 17.5-53.25 35.25-74.5 5-5.75 10.5-11 15.25-16.5 10.5-12.25 17-29 17-45zM256 144c0 25.75-8.5 48-25.75 67s-40 45.75-42 72.5c7.25 4.25 11.75 12.25 11.75 20.5 0 6-2.25 11.75-6.25 16 4 4.25 6.25 10 6.25 16 0 8.25-4.25 15.75-11.25 20.25 2 3.5 3.25 7.75 3.25 11.75 0 16.25-12.75 24-27.25 24-6.5 14.5-21 24-36.75 24s-30.25-9.5-36.75-24c-14.5 0-27.25-7.75-27.25-24 0-4 1.25-8.25 3.25-11.75-7-4.5-11.25-12-11.25-20.25 0-6 2.25-11.75 6.25-16-4-4.25-6.25-10-6.25-16 0-8.25 4.5-16.25 11.75-20.5-2-26.75-24.75-53.5-42-72.5s-25.75-41.25-25.75-67c0-68 64.75-112 128-112s128 44 128 112z"></path></svg></span><span class="pojo-a11y-toolbar-text">Light Background</span> </a> </li> <li class="pojo-a11y-toolbar-item"> <a href="#" class="pojo-a11y-toolbar-link pojo-a11y-btn-links-underline" data-action="links-underline" data-action-group="toggle" tabindex="-1" role="button"> <span class="pojo-a11y-toolbar-icon"><svg version="1.1" xmlns="http://www.w3.org/2000/svg" width="1em" viewBox="0 0 448 448"><title>Links Underline</title><path fill="currentColor" d="M364 304c0-6.5-2.5-12.5-7-17l-52-52c-4.5-4.5-10.75-7-17-7-7.25 0-13 2.75-18 8 8.25 8.25 18 15.25 18 28 0 13.25-10.75 24-24 24-12.75 0-19.75-9.75-28-18-5.25 5-8.25 10.75-8.25 18.25 0 6.25 2.5 12.5 7 17l51.5 51.75c4.5 4.5 10.75 6.75 17 6.75s12.5-2.25 17-6.5l36.75-36.5c4.5-4.5 7-10.5 7-16.75zM188.25 127.75c0-6.25-2.5-12.5-7-17l-51.5-51.75c-4.5-4.5-10.75-7-17-7s-12.5 2.5-17 6.75l-36.75 36.5c-4.5 4.5-7 10.5-7 16.75 0 6.5 2.5 12.5 7 17l52 52c4.5 4.5 10.75 6.75 17 6.75 7.25 0 13-2.5 18-7.75-8.25-8.25-18-15.25-18-28 0-13.25 10.75-24 24-24 12.75 0 19.75 9.75 28 18 5.25-5 8.25-10.75 8.25-18.25zM412 304c0 19-7.75 37.5-21.25 50.75l-36.75 36.5c-13.5 13.5-31.75 20.75-50.75 20.75-19.25 0-37.5-7.5-51-21.25l-51.5-51.75c-13.5-13.5-20.75-31.75-20.75-50.75 0-19.75 8-38.5 22-52.25l-22-22c-13.75 14-32.25 22-52 22-19 0-37.5-7.5-51-21l-52-52c-13.75-13.75-21-31.75-21-51 0-19 7.75-37.5 21.25-50.75l36.75-36.5c13.5-13.5 31.75-20.75 50.75-20.75 19.25 0 37.5 7.5 51 21.25l51.5 51.75c13.5 13.5 20.75 31.75 20.75 50.75 0 19.75-8 38.5-22 52.25l22 22c13.75-14 32.25-22 52-22 19 0 37.5 7.5 51 21l52 52c13.75 13.75 21 31.75 21 51z"></path></svg></span><span class="pojo-a11y-toolbar-text">Links Underline</span> </a> </li> <li class="pojo-a11y-toolbar-item"> <a href="#" class="pojo-a11y-toolbar-link pojo-a11y-btn-readable-font" data-action="readable-font" data-action-group="toggle" tabindex="-1" role="button"> <span class="pojo-a11y-toolbar-icon"><svg version="1.1" xmlns="http://www.w3.org/2000/svg" width="1em" viewBox="0 0 448 448"><title>Readable Font</title><path fill="currentColor" d="M181.25 139.75l-42.5 112.5c24.75 0.25 49.5 1 74.25 1 4.75 0 9.5-0.25 14.25-0.5-13-38-28.25-76.75-46-113zM0 416l0.5-19.75c23.5-7.25 49-2.25 59.5-29.25l59.25-154 70-181h32c1 1.75 2 3.5 2.75 5.25l51.25 120c18.75 44.25 36 89 55 133 11.25 26 20 52.75 32.5 78.25 1.75 4 5.25 11.5 8.75 14.25 8.25 6.5 31.25 8 43 12.5 0.75 4.75 1.5 9.5 1.5 14.25 0 2.25-0.25 4.25-0.25 6.5-31.75 0-63.5-4-95.25-4-32.75 0-65.5 2.75-98.25 3.75 0-6.5 0.25-13 1-19.5l32.75-7c6.75-1.5 20-3.25 20-12.5 0-9-32.25-83.25-36.25-93.5l-112.5-0.5c-6.5 14.5-31.75 80-31.75 89.5 0 19.25 36.75 20 51 22 0.25 4.75 0.25 9.5 0.25 14.5 0 2.25-0.25 4.5-0.5 6.75-29 0-58.25-5-87.25-5-3.5 0-8.5 1.5-12 2-15.75 2.75-31.25 3.5-47 3.5z"></path></svg></span><span class="pojo-a11y-toolbar-text">Readable Font</span> </a> </li> <li class="pojo-a11y-toolbar-item"> <a href="#" class="pojo-a11y-toolbar-link pojo-a11y-btn-reset" data-action="reset" tabindex="-1" role="button"> <span class="pojo-a11y-toolbar-icon"><svg version="1.1" xmlns="http://www.w3.org/2000/svg" width="1em" viewBox="0 0 448 448"><title>Reset</title><path fill="currentColor" d="M384 224c0 105.75-86.25 192-192 192-57.25 0-111.25-25.25-147.75-69.25-2.5-3.25-2.25-8 0.5-10.75l34.25-34.5c1.75-1.5 4-2.25 6.25-2.25 2.25 0.25 4.5 1.25 5.75 3 24.5 31.75 61.25 49.75 101 49.75 70.5 0 128-57.5 128-128s-57.5-128-128-128c-32.75 0-63.75 12.5-87 34.25l34.25 34.5c4.75 4.5 6 11.5 3.5 17.25-2.5 6-8.25 10-14.75 10h-112c-8.75 0-16-7.25-16-16v-112c0-6.5 4-12.25 10-14.75 5.75-2.5 12.75-1.25 17.25 3.5l32.5 32.25c35.25-33.25 83-53 132.25-53 105.75 0 192 86.25 192 192z"></path></svg></span> <span class="pojo-a11y-toolbar-text">Reset</span> </a> </li> </ul> </div> </div> </nav> </body> </html>

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