/ en Thu, 09 Apr 26 14:00:36 -0400 /news/leukemia-cells-use-sugar-coated-protein-hide-immune-system <span class="field field--name-title field--type-string field--label-hidden"><h1>Leukemia cells use a sugar-coated protein to hide from the immune system</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Corie Lok</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-09T14:00:36-04:00" class="datetime">April 9, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Leukemia cells use a sugar-coated protein to hide from the immune system</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Targeting this protein, called CD43, could offer a new path to treatment for leukemia and other cancers.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Sarah C.P. Williams </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-09T14:00:36-04:00" title="Thursday, April 9, 2026 - 14:00" class="datetime">April 9, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=7L5nH3Th 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=7L5nH3Th 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=Yg94mfRJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=j7upqT_f 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=BmLFekuu 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=6LdCUS6y 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=6LdCUS6y" alt="Illustration of a white leukemia cells with a sugary protein "shield" that is preventing a blue macrophage cell from killing it" title="Illustration of a white leukemia cells with a sugary protein "shield" that is preventing a blue macrophage cell from killing it" typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Mounica Vallurupalli </div> <div class="media-caption__description"> Leukemia cells (right) use a sugary protein coating as a shield against the immune system’s macrophages (left). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/941/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/941/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/941/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1" data-list-item-id="e95e815da2b5dbeb89b8b9092c4155be6">Study reveals previously unrecognized way for cancer to evade the immune system. </li> <li aria-level="1" data-list-item-id="ee30d13b122fcf60936f39de395491730">Other cancers could also be using sugar-coated proteins to shield themselves from immune attack.</li> <li aria-level="1" data-list-item-id="ee6df1f5014645fe07dc6cec6b424d93d">Findings suggest CD43 is a potential target for new cancer immunotherapies.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related News</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/cancer-immunotherapy-candidate-provokes-powerful-dual-response-cancer-and-immune-cells" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/cancer-immunotherapy-candidate-provokes-powerful-dual-response-cancer-and-immune-cells"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/p2_main_0.png?itok=LmB4RTrP 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/p2_main_0.png?itok=LmB4RTrP 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/p2_main_0.png?itok=Y9KtLDw5 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/p2_main_0.png?itok=Y9KtLDw5 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/p2_main_0.png?itok=bIRHRUgu 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/p2_main_0.png?itok=dvLmRKa1 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/p2_main_0.png?itok=dvLmRKa1" alt="Protein diagram showing the new small molecule inhibitor nestled inside the PTPN2 protein." title="Protein diagram showing the new small molecule inhibitor nestled inside the PTPN2 protein." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/cancer-immunotherapy-candidate-provokes-powerful-dual-response-cancer-and-immune-cells" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Cancer immunotherapy candidate provokes powerful dual response in cancer and immune cells</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Leukemia is adept at dodging the immune system, making it resistant to many of the newest generation of cancer immunotherapies. Now, researchers have identified a key part of the cancer’s disguise: a protein called CD43 on the surface of leukemia cells that is coated so heavily in sugar molecules that it forms a physical barrier, shielding the cells from immune attack.</p> <p>The findings, from scientists at the ӳ����ý, Mass General Brigham, and Dana-Farber Cancer Institute, reveal a previously unrecognized way that cancer evades the immune system and could point toward new immunotherapies that block CD43 to expose cancer cells to immune attack.</p> <p>“Discovering this phenomenon opens up a new avenue for cancer immunotherapy,” said <a href="/bios/todd-r-golub">Todd Golub</a>, a Dana-Farber pediatric oncologist, director of the ӳ����ý and co-senior author of the study published in <a target="_blank" href="https://www.science.org/doi/10.1126/science.ady5196"><em>Science</em></a>. “We think that the concept of cancers hiding behind sugar-coated proteins is not only important for leukemia, but likely other cancers as well.”</p> <p>The team made this discovery by examining thousands of genes across the whole genome in leukemia cells, which uncovered a surprise about another protein called CD47 — the most well-known “don't-eat-me” signal used by cancers. They found that it had little effect on whether immune cells could destroy leukemia cells. The result could help explain why experimental drugs targeting CD47 have largely failed in clinical trials for patients with AML.</p> <p>“We designed this experiment fully expecting that CD47 would be the most important protein for blocking the immune system,” said <a href="/bios/robert-manguso">Robert Manguso</a>, an associate member of the ӳ����ý and researcher at the <a target="_blank" href="https://www.massgeneral.org/cancer-center/clinical-trials-and-research/center-for-cancer-research?cmp=nwsref">Krantz Family Center for Cancer Research</a> with Mass General Brigham Cancer Institute, who co-led the study. “When it barely registered, we thought we’d made a mistake. We repeated the experiments over and over. But we kept getting the same answer.”</p> <h2>New options for AML</h2> <p>The new study arose out of conversations between the study’s co-first authors Jooho Chung, a postdoctoral researcher in the Manguso lab and a medical oncologist at Mass General Brigham Cancer Institute, and Mounica Vallurupalli, a Dana-Farber medical oncologist and postdoctoral researcher in the Golub lab at the ӳ����ý. Both physician-scientists were frustrated by the lack of options for their acute myeloid leukemia (AML) patients.</p> <p>“We know that leukemia can be susceptible to immune attack, but we also know that most cases of AML don’t respond to the newer immunotherapies that have worked so well in other cancers,” said Chung. “We wanted to understand why.”</p> <p>The researchers conducted a genome-wide CRISPR screen, disabling thousands of genes one-by-one in millions of human AML cells. Then, they tested which cells were recognized by macrophages—immune cells that patrol the body and destroy foreign or dangerous cells by engulfing them.</p> <p>They found that AML cells that were missing CD43 were engulfed at dramatically higher rates than cells with functioning CD43. Cells lacking genes needed to coat CD43 with a sugar called sialic acid showed the same pattern. The results suggested that it was the sialic acid coating on CD43 that was protecting AML cells from macrophages.</p> <p>Further experiments ruled out the possibility that CD43 was sending a specific molecular “don't-eat-me” signal to macrophages and pointed instead to a physical explanation for its ability to block immune reactions. The team suspected that the high levels of sugar-coated CD43 were completely blocking the ability of immune cells to get close to the surface of AML cells. <br>Indeed, when Chung and Vallurupalli created progressively shorter versions of CD43 on AML cells, macrophages could more easily engulf the cells. The shorter the protein, the more effective the immune attack.</p> <p>The team looked at other cancer-killing immune cells — T cells and NK cells — and discovered that inhibiting CD43 also enhanced their ability to attack AML cells.</p> <p>“In every case we tried, all types of immune cells that need direct access to the cell surface were inhibited by high levels of CD43. And that really lent even more credibility to the idea that this is a physical barrier and not a specific interaction between a receptor and ligand,” Manguso said.</p> <h2>Toward new treatments</h2> <p>The researchers believe other cancers could also be covering themselves in large, sugar-coated proteins to fend off the immune system. When they replaced CD43 in AML cells with MUC1—a sugar-coated protein abundant in several cancer types—it produced the same barrier effect.</p> <p>“We think we’re looking at a foundational layer of immune evasion that may be operating in nearly all cancers,” said Manguso. “Figuring out how to dismantle it has implications for cancer immunotherapy well beyond leukemia.”</p> <p>The researchers are now exploring possible new treatments for AML by looking for antibodies that bind to CD43. In the lab, they found that this approach made it easier for macrophages to recognize and engulf AML cells.</p> <p>“If we could block CD43 in just the right way, that could go a long way to developing a new therapeutic strategy to kill these cancer cells and treat leukemia,” Vallurupalli said.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for the study was provided by the National Institutes of Health, Calico Life Sciences, a Jonathan Kraft Translational Team Research Award, the Damon Runyon Cancer Research Foundation, the Edward P. Evans Foundation, and the Polish National Agency for Academic Exchange.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited:</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Chung J, Vallurupalli M, et al. <a target="_blank" href="https://www.science.org/doi/10.1126/science.ady5196">Sialylated CD43 forms a glyco-immune barrier that restrains anti-leukemic immunity</a>. <em>Science</em>. Online April 9, 2026. DOI: 10.1126/science.ady5196</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/broad-tags/therapeutic-response" hreflang="en">Therapeutics</a></div> </div> </div> </div> </div> </div> Thu, 09 Apr 2026 18:00:36 +0000 Corie Lok 5560351 at /news/scientists-develop-molecules-may-treat-crohns-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Leukemia cells use a sugar-coated protein to hide from the immune system</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Corie Lok</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-09T14:00:36-04:00" class="datetime">April 9, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Leukemia cells use a sugar-coated protein to hide from the immune system</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Targeting this protein, called CD43, could offer a new path to treatment for leukemia and other cancers.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Sarah C.P. Williams </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-09T14:00:36-04:00" title="Thursday, April 9, 2026 - 14:00" class="datetime">April 9, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=7L5nH3Th 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=7L5nH3Th 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=Yg94mfRJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=j7upqT_f 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=BmLFekuu 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=6LdCUS6y 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=6LdCUS6y" alt="Illustration of a white leukemia cells with a sugary protein "shield" that is preventing a blue macrophage cell from killing it" title="Illustration of a white leukemia cells with a sugary protein "shield" that is preventing a blue macrophage cell from killing it" typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Mounica Vallurupalli </div> <div class="media-caption__description"> Leukemia cells (right) use a sugary protein coating as a shield against the immune system’s macrophages (left). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/941/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a 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field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1" data-list-item-id="e95e815da2b5dbeb89b8b9092c4155be6">Study reveals previously unrecognized way for cancer to evade the immune system. </li> <li aria-level="1" data-list-item-id="ee30d13b122fcf60936f39de395491730">Other cancers could also be using sugar-coated proteins to shield themselves from immune attack.</li> <li aria-level="1" data-list-item-id="ee6df1f5014645fe07dc6cec6b424d93d">Findings suggest CD43 is a potential target for new cancer immunotherapies.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related News</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/cancer-immunotherapy-candidate-provokes-powerful-dual-response-cancer-and-immune-cells" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/cancer-immunotherapy-candidate-provokes-powerful-dual-response-cancer-and-immune-cells"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/p2_main_0.png?itok=LmB4RTrP 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/p2_main_0.png?itok=LmB4RTrP 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/p2_main_0.png?itok=Y9KtLDw5 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/p2_main_0.png?itok=Y9KtLDw5 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/p2_main_0.png?itok=bIRHRUgu 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/p2_main_0.png?itok=dvLmRKa1 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/p2_main_0.png?itok=dvLmRKa1" alt="Protein diagram showing the new small molecule inhibitor nestled inside the PTPN2 protein." title="Protein diagram showing the new small molecule inhibitor nestled inside the PTPN2 protein." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/cancer-immunotherapy-candidate-provokes-powerful-dual-response-cancer-and-immune-cells" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Cancer immunotherapy candidate provokes powerful dual response in cancer and immune cells</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Leukemia is adept at dodging the immune system, making it resistant to many of the newest generation of cancer immunotherapies. Now, researchers have identified a key part of the cancer’s disguise: a protein called CD43 on the surface of leukemia cells that is coated so heavily in sugar molecules that it forms a physical barrier, shielding the cells from immune attack.</p> <p>The findings, from scientists at the ӳ����ý, Mass General Brigham, and Dana-Farber Cancer Institute, reveal a previously unrecognized way that cancer evades the immune system and could point toward new immunotherapies that block CD43 to expose cancer cells to immune attack.</p> <p>“Discovering this phenomenon opens up a new avenue for cancer immunotherapy,” said <a href="/bios/todd-r-golub">Todd Golub</a>, a Dana-Farber pediatric oncologist, director of the ӳ����ý and co-senior author of the study published in <a target="_blank" href="https://www.science.org/doi/10.1126/science.ady5196"><em>Science</em></a>. “We think that the concept of cancers hiding behind sugar-coated proteins is not only important for leukemia, but likely other cancers as well.”</p> <p>The team made this discovery by examining thousands of genes across the whole genome in leukemia cells, which uncovered a surprise about another protein called CD47 — the most well-known “don't-eat-me” signal used by cancers. They found that it had little effect on whether immune cells could destroy leukemia cells. The result could help explain why experimental drugs targeting CD47 have largely failed in clinical trials for patients with AML.</p> <p>“We designed this experiment fully expecting that CD47 would be the most important protein for blocking the immune system,” said <a href="/bios/robert-manguso">Robert Manguso</a>, an associate member of the ӳ����ý and researcher at the <a target="_blank" href="https://www.massgeneral.org/cancer-center/clinical-trials-and-research/center-for-cancer-research?cmp=nwsref">Krantz Family Center for Cancer Research</a> with Mass General Brigham Cancer Institute, who co-led the study. “When it barely registered, we thought we’d made a mistake. We repeated the experiments over and over. But we kept getting the same answer.”</p> <h2>New options for AML</h2> <p>The new study arose out of conversations between the study’s co-first authors Jooho Chung, a postdoctoral researcher in the Manguso lab and a medical oncologist at Mass General Brigham Cancer Institute, and Mounica Vallurupalli, a Dana-Farber medical oncologist and postdoctoral researcher in the Golub lab at the ӳ����ý. Both physician-scientists were frustrated by the lack of options for their acute myeloid leukemia (AML) patients.</p> <p>“We know that leukemia can be susceptible to immune attack, but we also know that most cases of AML don’t respond to the newer immunotherapies that have worked so well in other cancers,” said Chung. “We wanted to understand why.”</p> <p>The researchers conducted a genome-wide CRISPR screen, disabling thousands of genes one-by-one in millions of human AML cells. Then, they tested which cells were recognized by macrophages—immune cells that patrol the body and destroy foreign or dangerous cells by engulfing them.</p> <p>They found that AML cells that were missing CD43 were engulfed at dramatically higher rates than cells with functioning CD43. Cells lacking genes needed to coat CD43 with a sugar called sialic acid showed the same pattern. The results suggested that it was the sialic acid coating on CD43 that was protecting AML cells from macrophages.</p> <p>Further experiments ruled out the possibility that CD43 was sending a specific molecular “don't-eat-me” signal to macrophages and pointed instead to a physical explanation for its ability to block immune reactions. The team suspected that the high levels of sugar-coated CD43 were completely blocking the ability of immune cells to get close to the surface of AML cells. <br>Indeed, when Chung and Vallurupalli created progressively shorter versions of CD43 on AML cells, macrophages could more easily engulf the cells. The shorter the protein, the more effective the immune attack.</p> <p>The team looked at other cancer-killing immune cells — T cells and NK cells — and discovered that inhibiting CD43 also enhanced their ability to attack AML cells.</p> <p>“In every case we tried, all types of immune cells that need direct access to the cell surface were inhibited by high levels of CD43. And that really lent even more credibility to the idea that this is a physical barrier and not a specific interaction between a receptor and ligand,” Manguso said.</p> <h2>Toward new treatments</h2> <p>The researchers believe other cancers could also be covering themselves in large, sugar-coated proteins to fend off the immune system. When they replaced CD43 in AML cells with MUC1—a sugar-coated protein abundant in several cancer types—it produced the same barrier effect.</p> <p>“We think we’re looking at a foundational layer of immune evasion that may be operating in nearly all cancers,” said Manguso. “Figuring out how to dismantle it has implications for cancer immunotherapy well beyond leukemia.”</p> <p>The researchers are now exploring possible new treatments for AML by looking for antibodies that bind to CD43. In the lab, they found that this approach made it easier for macrophages to recognize and engulf AML cells.</p> <p>“If we could block CD43 in just the right way, that could go a long way to developing a new therapeutic strategy to kill these cancer cells and treat leukemia,” Vallurupalli said.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for the study was provided by the National Institutes of Health, Calico Life Sciences, a Jonathan Kraft Translational Team Research Award, the Damon Runyon Cancer Research Foundation, the Edward P. Evans Foundation, and the Polish National Agency for Academic Exchange.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited:</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Chung J, Vallurupalli M, et al. <a target="_blank" href="https://www.science.org/doi/10.1126/science.ady5196">Sialylated CD43 forms a glyco-immune barrier that restrains anti-leukemic immunity</a>. <em>Science</em>. Online April 9, 2026. DOI: 10.1126/science.ady5196</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/broad-tags/therapeutic-response" hreflang="en">Therapeutics</a></div> </div> </div> </div> </div> </div> Fri, 16 Jan 2026 16:39:11 +0000 Corie Lok 5560116 at /news/de-risking-drug-discovery-predictive-ai <span class="field field--name-title field--type-string field--label-hidden"><h1>Leukemia cells use a sugar-coated protein to hide from the immune system</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Corie Lok</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-09T14:00:36-04:00" class="datetime">April 9, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Leukemia cells use a sugar-coated protein to hide from the immune system</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Targeting this protein, called CD43, could offer a new path to treatment for leukemia and other cancers.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Sarah C.P. Williams </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-09T14:00:36-04:00" title="Thursday, April 9, 2026 - 14:00" class="datetime">April 9, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=7L5nH3Th 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=7L5nH3Th 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=Yg94mfRJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=j7upqT_f 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=BmLFekuu 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=6LdCUS6y 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=6LdCUS6y" alt="Illustration of a white leukemia cells with a sugary protein "shield" that is preventing a blue macrophage cell from killing it" title="Illustration of a white leukemia cells with a sugary protein "shield" that is preventing a blue macrophage cell from killing it" typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Mounica Vallurupalli </div> <div class="media-caption__description"> Leukemia cells (right) use a sugary protein coating as a shield against the immune system’s macrophages (left). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/941/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/941/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/941/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1" data-list-item-id="e95e815da2b5dbeb89b8b9092c4155be6">Study reveals previously unrecognized way for cancer to evade the immune system. </li> <li aria-level="1" data-list-item-id="ee30d13b122fcf60936f39de395491730">Other cancers could also be using sugar-coated proteins to shield themselves from immune attack.</li> <li aria-level="1" data-list-item-id="ee6df1f5014645fe07dc6cec6b424d93d">Findings suggest CD43 is a potential target for new cancer immunotherapies.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related News</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/cancer-immunotherapy-candidate-provokes-powerful-dual-response-cancer-and-immune-cells" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/cancer-immunotherapy-candidate-provokes-powerful-dual-response-cancer-and-immune-cells"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/p2_main_0.png?itok=LmB4RTrP 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/p2_main_0.png?itok=LmB4RTrP 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/p2_main_0.png?itok=Y9KtLDw5 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/p2_main_0.png?itok=Y9KtLDw5 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/p2_main_0.png?itok=bIRHRUgu 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/p2_main_0.png?itok=dvLmRKa1 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/p2_main_0.png?itok=dvLmRKa1" alt="Protein diagram showing the new small molecule inhibitor nestled inside the PTPN2 protein." title="Protein diagram showing the new small molecule inhibitor nestled inside the PTPN2 protein." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/cancer-immunotherapy-candidate-provokes-powerful-dual-response-cancer-and-immune-cells" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Cancer immunotherapy candidate provokes powerful dual response in cancer and immune cells</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Leukemia is adept at dodging the immune system, making it resistant to many of the newest generation of cancer immunotherapies. Now, researchers have identified a key part of the cancer’s disguise: a protein called CD43 on the surface of leukemia cells that is coated so heavily in sugar molecules that it forms a physical barrier, shielding the cells from immune attack.</p> <p>The findings, from scientists at the ӳ����ý, Mass General Brigham, and Dana-Farber Cancer Institute, reveal a previously unrecognized way that cancer evades the immune system and could point toward new immunotherapies that block CD43 to expose cancer cells to immune attack.</p> <p>“Discovering this phenomenon opens up a new avenue for cancer immunotherapy,” said <a href="/bios/todd-r-golub">Todd Golub</a>, a Dana-Farber pediatric oncologist, director of the ӳ����ý and co-senior author of the study published in <a target="_blank" href="https://www.science.org/doi/10.1126/science.ady5196"><em>Science</em></a>. “We think that the concept of cancers hiding behind sugar-coated proteins is not only important for leukemia, but likely other cancers as well.”</p> <p>The team made this discovery by examining thousands of genes across the whole genome in leukemia cells, which uncovered a surprise about another protein called CD47 — the most well-known “don't-eat-me” signal used by cancers. They found that it had little effect on whether immune cells could destroy leukemia cells. The result could help explain why experimental drugs targeting CD47 have largely failed in clinical trials for patients with AML.</p> <p>“We designed this experiment fully expecting that CD47 would be the most important protein for blocking the immune system,” said <a href="/bios/robert-manguso">Robert Manguso</a>, an associate member of the ӳ����ý and researcher at the <a target="_blank" href="https://www.massgeneral.org/cancer-center/clinical-trials-and-research/center-for-cancer-research?cmp=nwsref">Krantz Family Center for Cancer Research</a> with Mass General Brigham Cancer Institute, who co-led the study. “When it barely registered, we thought we’d made a mistake. We repeated the experiments over and over. But we kept getting the same answer.”</p> <h2>New options for AML</h2> <p>The new study arose out of conversations between the study’s co-first authors Jooho Chung, a postdoctoral researcher in the Manguso lab and a medical oncologist at Mass General Brigham Cancer Institute, and Mounica Vallurupalli, a Dana-Farber medical oncologist and postdoctoral researcher in the Golub lab at the ӳ����ý. Both physician-scientists were frustrated by the lack of options for their acute myeloid leukemia (AML) patients.</p> <p>“We know that leukemia can be susceptible to immune attack, but we also know that most cases of AML don’t respond to the newer immunotherapies that have worked so well in other cancers,” said Chung. “We wanted to understand why.”</p> <p>The researchers conducted a genome-wide CRISPR screen, disabling thousands of genes one-by-one in millions of human AML cells. Then, they tested which cells were recognized by macrophages—immune cells that patrol the body and destroy foreign or dangerous cells by engulfing them.</p> <p>They found that AML cells that were missing CD43 were engulfed at dramatically higher rates than cells with functioning CD43. Cells lacking genes needed to coat CD43 with a sugar called sialic acid showed the same pattern. The results suggested that it was the sialic acid coating on CD43 that was protecting AML cells from macrophages.</p> <p>Further experiments ruled out the possibility that CD43 was sending a specific molecular “don't-eat-me” signal to macrophages and pointed instead to a physical explanation for its ability to block immune reactions. The team suspected that the high levels of sugar-coated CD43 were completely blocking the ability of immune cells to get close to the surface of AML cells. <br>Indeed, when Chung and Vallurupalli created progressively shorter versions of CD43 on AML cells, macrophages could more easily engulf the cells. The shorter the protein, the more effective the immune attack.</p> <p>The team looked at other cancer-killing immune cells — T cells and NK cells — and discovered that inhibiting CD43 also enhanced their ability to attack AML cells.</p> <p>“In every case we tried, all types of immune cells that need direct access to the cell surface were inhibited by high levels of CD43. And that really lent even more credibility to the idea that this is a physical barrier and not a specific interaction between a receptor and ligand,” Manguso said.</p> <h2>Toward new treatments</h2> <p>The researchers believe other cancers could also be covering themselves in large, sugar-coated proteins to fend off the immune system. When they replaced CD43 in AML cells with MUC1—a sugar-coated protein abundant in several cancer types—it produced the same barrier effect.</p> <p>“We think we’re looking at a foundational layer of immune evasion that may be operating in nearly all cancers,” said Manguso. “Figuring out how to dismantle it has implications for cancer immunotherapy well beyond leukemia.”</p> <p>The researchers are now exploring possible new treatments for AML by looking for antibodies that bind to CD43. In the lab, they found that this approach made it easier for macrophages to recognize and engulf AML cells.</p> <p>“If we could block CD43 in just the right way, that could go a long way to developing a new therapeutic strategy to kill these cancer cells and treat leukemia,” Vallurupalli said.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for the study was provided by the National Institutes of Health, Calico Life Sciences, a Jonathan Kraft Translational Team Research Award, the Damon Runyon Cancer Research Foundation, the Edward P. Evans Foundation, and the Polish National Agency for Academic Exchange.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited:</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Chung J, Vallurupalli M, et al. <a target="_blank" href="https://www.science.org/doi/10.1126/science.ady5196">Sialylated CD43 forms a glyco-immune barrier that restrains anti-leukemic immunity</a>. <em>Science</em>. Online April 9, 2026. DOI: 10.1126/science.ady5196</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/broad-tags/therapeutic-response" hreflang="en">Therapeutics</a></div> </div> </div> </div> </div> </div> Wed, 17 Jul 2024 19:00:47 +0000 tulrich@broadinstitute.org 5557131 at /news/therapy-candidate-fatal-prion-diseases-turns-disease-causing-gene <span class="field field--name-title field--type-string field--label-hidden"><h1>Leukemia cells use a sugar-coated protein to hide from the immune system</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Corie Lok</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-09T14:00:36-04:00" class="datetime">April 9, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Leukemia cells use a sugar-coated protein to hide from the immune system</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Targeting this protein, called CD43, could offer a new path to treatment for leukemia and other cancers.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Sarah C.P. Williams </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-09T14:00:36-04:00" title="Thursday, April 9, 2026 - 14:00" class="datetime">April 9, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=7L5nH3Th 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=7L5nH3Th 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=Yg94mfRJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=j7upqT_f 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=BmLFekuu 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=6LdCUS6y 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/CD43_Main%20News%20Story%20%281%29%20%281%29.png?h=a7d067a7&itok=6LdCUS6y" alt="Illustration of a white leukemia cells with a sugary protein "shield" that is preventing a blue macrophage cell from killing it" title="Illustration of a white leukemia cells with a sugary protein "shield" that is preventing a blue macrophage cell from killing it" typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Mounica Vallurupalli </div> <div class="media-caption__description"> Leukemia cells (right) use a sugary protein coating as a shield against the immune system’s macrophages (left). </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/941/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/941/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/941/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1" data-list-item-id="e95e815da2b5dbeb89b8b9092c4155be6">Study reveals previously unrecognized way for cancer to evade the immune system. </li> <li aria-level="1" data-list-item-id="ee30d13b122fcf60936f39de395491730">Other cancers could also be using sugar-coated proteins to shield themselves from immune attack.</li> <li aria-level="1" data-list-item-id="ee6df1f5014645fe07dc6cec6b424d93d">Findings suggest CD43 is a potential target for new cancer immunotherapies.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related News</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/cancer-immunotherapy-candidate-provokes-powerful-dual-response-cancer-and-immune-cells" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/cancer-immunotherapy-candidate-provokes-powerful-dual-response-cancer-and-immune-cells"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/p2_main_0.png?itok=LmB4RTrP 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/p2_main_0.png?itok=LmB4RTrP 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/p2_main_0.png?itok=Y9KtLDw5 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/p2_main_0.png?itok=Y9KtLDw5 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/p2_main_0.png?itok=bIRHRUgu 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/p2_main_0.png?itok=dvLmRKa1 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/p2_main_0.png?itok=dvLmRKa1" alt="Protein diagram showing the new small molecule inhibitor nestled inside the PTPN2 protein." title="Protein diagram showing the new small molecule inhibitor nestled inside the PTPN2 protein." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/cancer-immunotherapy-candidate-provokes-powerful-dual-response-cancer-and-immune-cells" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Cancer immunotherapy candidate provokes powerful dual response in cancer and immune cells</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Leukemia is adept at dodging the immune system, making it resistant to many of the newest generation of cancer immunotherapies. Now, researchers have identified a key part of the cancer’s disguise: a protein called CD43 on the surface of leukemia cells that is coated so heavily in sugar molecules that it forms a physical barrier, shielding the cells from immune attack.</p> <p>The findings, from scientists at the ӳ����ý, Mass General Brigham, and Dana-Farber Cancer Institute, reveal a previously unrecognized way that cancer evades the immune system and could point toward new immunotherapies that block CD43 to expose cancer cells to immune attack.</p> <p>“Discovering this phenomenon opens up a new avenue for cancer immunotherapy,” said <a href="/bios/todd-r-golub">Todd Golub</a>, a Dana-Farber pediatric oncologist, director of the ӳ����ý and co-senior author of the study published in <a target="_blank" href="https://www.science.org/doi/10.1126/science.ady5196"><em>Science</em></a>. “We think that the concept of cancers hiding behind sugar-coated proteins is not only important for leukemia, but likely other cancers as well.”</p> <p>The team made this discovery by examining thousands of genes across the whole genome in leukemia cells, which uncovered a surprise about another protein called CD47 — the most well-known “don't-eat-me” signal used by cancers. They found that it had little effect on whether immune cells could destroy leukemia cells. The result could help explain why experimental drugs targeting CD47 have largely failed in clinical trials for patients with AML.</p> <p>“We designed this experiment fully expecting that CD47 would be the most important protein for blocking the immune system,” said <a href="/bios/robert-manguso">Robert Manguso</a>, an associate member of the ӳ����ý and researcher at the <a target="_blank" href="https://www.massgeneral.org/cancer-center/clinical-trials-and-research/center-for-cancer-research?cmp=nwsref">Krantz Family Center for Cancer Research</a> with Mass General Brigham Cancer Institute, who co-led the study. “When it barely registered, we thought we’d made a mistake. We repeated the experiments over and over. But we kept getting the same answer.”</p> <h2>New options for AML</h2> <p>The new study arose out of conversations between the study’s co-first authors Jooho Chung, a postdoctoral researcher in the Manguso lab and a medical oncologist at Mass General Brigham Cancer Institute, and Mounica Vallurupalli, a Dana-Farber medical oncologist and postdoctoral researcher in the Golub lab at the ӳ����ý. Both physician-scientists were frustrated by the lack of options for their acute myeloid leukemia (AML) patients.</p> <p>“We know that leukemia can be susceptible to immune attack, but we also know that most cases of AML don’t respond to the newer immunotherapies that have worked so well in other cancers,” said Chung. “We wanted to understand why.”</p> <p>The researchers conducted a genome-wide CRISPR screen, disabling thousands of genes one-by-one in millions of human AML cells. Then, they tested which cells were recognized by macrophages—immune cells that patrol the body and destroy foreign or dangerous cells by engulfing them.</p> <p>They found that AML cells that were missing CD43 were engulfed at dramatically higher rates than cells with functioning CD43. Cells lacking genes needed to coat CD43 with a sugar called sialic acid showed the same pattern. The results suggested that it was the sialic acid coating on CD43 that was protecting AML cells from macrophages.</p> <p>Further experiments ruled out the possibility that CD43 was sending a specific molecular “don't-eat-me” signal to macrophages and pointed instead to a physical explanation for its ability to block immune reactions. The team suspected that the high levels of sugar-coated CD43 were completely blocking the ability of immune cells to get close to the surface of AML cells. <br>Indeed, when Chung and Vallurupalli created progressively shorter versions of CD43 on AML cells, macrophages could more easily engulf the cells. The shorter the protein, the more effective the immune attack.</p> <p>The team looked at other cancer-killing immune cells — T cells and NK cells — and discovered that inhibiting CD43 also enhanced their ability to attack AML cells.</p> <p>“In every case we tried, all types of immune cells that need direct access to the cell surface were inhibited by high levels of CD43. And that really lent even more credibility to the idea that this is a physical barrier and not a specific interaction between a receptor and ligand,” Manguso said.</p> <h2>Toward new treatments</h2> <p>The researchers believe other cancers could also be covering themselves in large, sugar-coated proteins to fend off the immune system. When they replaced CD43 in AML cells with MUC1—a sugar-coated protein abundant in several cancer types—it produced the same barrier effect.</p> <p>“We think we’re looking at a foundational layer of immune evasion that may be operating in nearly all cancers,” said Manguso. “Figuring out how to dismantle it has implications for cancer immunotherapy well beyond leukemia.”</p> <p>The researchers are now exploring possible new treatments for AML by looking for antibodies that bind to CD43. In the lab, they found that this approach made it easier for macrophages to recognize and engulf AML cells.</p> <p>“If we could block CD43 in just the right way, that could go a long way to developing a new therapeutic strategy to kill these cancer cells and treat leukemia,” Vallurupalli said.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for the study was provided by the National Institutes of Health, Calico Life Sciences, a Jonathan Kraft Translational Team Research Award, the Damon Runyon Cancer Research Foundation, the Edward P. Evans Foundation, and the Polish National Agency for Academic Exchange.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited:</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Chung J, Vallurupalli M, et al. <a target="_blank" href="https://www.science.org/doi/10.1126/science.ady5196">Sialylated CD43 forms a glyco-immune barrier that restrains anti-leukemic immunity</a>. <em>Science</em>. Online April 9, 2026. DOI: 10.1126/science.ady5196</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/broad-tags/therapeutic-response" hreflang="en">Therapeutics</a></div> </div> </div> </div> </div> </div> Thu, 27 Jun 2024 18:11:10 +0000 Corie Lok 5557021 at