{"id":41930,"date":"2025-09-02T02:51:17","date_gmt":"2025-09-02T00:51:17","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/09\/02\/tumor-derived-ebi3-promotes-cd8-t-cell-exhaustion-via-stat4-il-10-ccl5-in-gastric-cancer\/"},"modified":"2025-09-02T02:51:17","modified_gmt":"2025-09-02T00:51:17","slug":"tumor-derived-ebi3-promotes-cd8-t-cell-exhaustion-via-stat4-il-10-ccl5-in-gastric-cancer","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/09\/02\/tumor-derived-ebi3-promotes-cd8-t-cell-exhaustion-via-stat4-il-10-ccl5-in-gastric-cancer\/","title":{"rendered":"Tumor-derived EBI3 promotes CD8+ T cell exhaustion via STAT4-IL-10\/CCL5 in gastric cancer"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Sep 1. doi: 10.1158\/2326-6066.CIR-24-1228. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Combination chemotherapy and immunotherapy are effective against advanced gastric cancer (GC). However, T cell exhaustion in the tumor microenvironment may decrease the immune response and compromise the effectiveness of immunotherapy. Herein, we report the potential role of EBI3 in promoting T cell exhaustion and its mechanism in GC, showing high expression of EBI3 in GC. Correlation analysis between EBI3 expression level and clinical-pathological features indicated significant associations with Tumor stage, Nodal staging, pathologic stage, and degree of tumor differentiation. EBI3 expression levels correlated with a state of high CD8+ T cell exhaustion, as identified by transcriptome sequencing and mice orthotopic GC models. On exposure to EBI3, CD8+ T cells showed signs of cell exhaustion as reduced cytokine secretion and increased expression of inhibitory receptors in vitro\/vivo studies. Mechanistically, EBI3 induced T cell exhaustion by promoting phosphorylation of STAT4, upregulating the transcription of downstream target genes CCL5 and IL-10. An anti-EBI3 heptapeptide (Val-Tyr-Leu-His-Trp-His-Asp) was developed, which competitively bound EBI3 and reversed the induction of T cell exhaustion. Taken together, we identified a T cell exhaustion mechanism in GC via the EBI3-STAT4-IL10\/CCL5 axis and developed an anti-EBI3 heptapeptide with an antagonistic function. These findings provide a potential immunotherapeutic target and support the development of EBI3-based interventions to enhance immunotherapy efficacy in GC.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40889276\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250901205114&amp;v=2.18.0.post9+e462414\">40889276<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-1228\">10.1158\/2326-6066.CIR-24-1228<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Sep 1. doi: 10.1158\/2326-6066.CIR-24-1228. Online ahead of print. ABSTRACT Combination chemotherapy and immunotherapy are effective against advanced gastric cancer (GC). However, T cell exhaustion in the tumor microenvironment may decrease the immune response and compromise the effectiveness of immunotherapy. Herein, we report the potential role of EBI3 in promoting T cell &#8230; <a title=\"Tumor-derived EBI3 promotes CD8+ T cell exhaustion via STAT4-IL-10\/CCL5 in gastric cancer\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/09\/02\/tumor-derived-ebi3-promotes-cd8-t-cell-exhaustion-via-stat4-il-10-ccl5-in-gastric-cancer\/\" aria-label=\"Read more about Tumor-derived EBI3 promotes CD8+ T cell exhaustion via STAT4-IL-10\/CCL5 in gastric cancer\">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-41930","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\/41930","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=41930"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/41930\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=41930"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=41930"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=41930"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}