{"id":41147,"date":"2025-08-19T18:47:42","date_gmt":"2025-08-19T16:47:42","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/08\/19\/reprogramming-cd8-t-cell-branched-n-glycosylation-limits-exhaustion-enhancing-cytotoxicity-and-tumor-killing\/"},"modified":"2025-08-19T18:47:42","modified_gmt":"2025-08-19T16:47:42","slug":"reprogramming-cd8-t-cell-branched-n-glycosylation-limits-exhaustion-enhancing-cytotoxicity-and-tumor-killing","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/08\/19\/reprogramming-cd8-t-cell-branched-n-glycosylation-limits-exhaustion-enhancing-cytotoxicity-and-tumor-killing\/","title":{"rendered":"Reprogramming CD8+ T-cell branched N-glycosylation limits exhaustion, enhancing cytotoxicity and tumor killing"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Aug 19. doi: 10.1158\/2326-6066.CIR-25-0313. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>T-cell therapies have transformed cancer treatment. While surface glycans have been shown to play critical roles in regulating T-cell development and function, whether and how the glycome influences T cell-mediated tumor immunity remains an area of active investigation. In this study, we show that the intratumoral T-cell glycome is altered early in human colorectal cancer, with substantial changes in branched N-glycans. We demonstrated that CD8+ T cells expressing \u03b21,6-GlcNAc branched N-glycans adopted an exhausted phenotype, marked by increased PD1 and Tim3 expression. CRISPR\/Cas9 deletion of key branching glycosyltransferase genes revealed that Mgat5 played a prominent role in T-cell exhaustion. In culture-based assays and tumor studies, Mgat5 deletion in CD8+ T cells resulted in improved cancer cell killing. These findings prompted assessment of whether MGAT5 deletion in anti-CD19 chimeric-antigen receptor (CAR) T cells could enable this therapeutic modality in a solid tumor setting. We showed that MGAT5 KO anti-CD19-CAR T cells inhibited the growth of CD19-transduced tumors. Together, these findings show that MGAT5-mediated branched N-glycans regulate CD8+ T-cell function in cancer and provide a strategy to enhance antitumor activity of native and CAR T cells.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40828448\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250819124738&amp;v=2.18.0.post9+e462414\">40828448<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-0313\">10.1158\/2326-6066.CIR-25-0313<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Aug 19. doi: 10.1158\/2326-6066.CIR-25-0313. Online ahead of print. ABSTRACT T-cell therapies have transformed cancer treatment. While surface glycans have been shown to play critical roles in regulating T-cell development and function, whether and how the glycome influences T cell-mediated tumor immunity remains an area of active investigation. In this study, we &#8230; <a title=\"Reprogramming CD8+ T-cell branched N-glycosylation limits exhaustion, enhancing cytotoxicity and tumor killing\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/08\/19\/reprogramming-cd8-t-cell-branched-n-glycosylation-limits-exhaustion-enhancing-cytotoxicity-and-tumor-killing\/\" aria-label=\"Read more about Reprogramming CD8+ T-cell branched N-glycosylation limits exhaustion, enhancing cytotoxicity and tumor killing\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-41147","post","type-post","status-publish","format-standard","hentry","category-cancer-immunology-reserch","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/41147","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=41147"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/41147\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=41147"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=41147"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=41147"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}