{"id":50083,"date":"2025-12-05T20:44:03","date_gmt":"2025-12-05T19:44:03","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/12\/05\/t-cell-priming-by-high-avidity-neoantigens-in-lymph-nodes-augments-adoptive-immunotherapy\/"},"modified":"2025-12-05T20:44:03","modified_gmt":"2025-12-05T19:44:03","slug":"t-cell-priming-by-high-avidity-neoantigens-in-lymph-nodes-augments-adoptive-immunotherapy","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/12\/05\/t-cell-priming-by-high-avidity-neoantigens-in-lymph-nodes-augments-adoptive-immunotherapy\/","title":{"rendered":"T cell priming by high avidity neoantigens in lymph nodes augments adoptive immunotherapy"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Dec 5. doi: 10.1158\/2326-6066.CIR-25-0514. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Adoptive transfer of T lymphocytes specific for tumor-associated neoantigens can elicit immunity against solid tumors in patients. However, how these antigens impact T cell function, effector differentiation, and persistence remains unclear. We examined how an identical CD8+ T cell product was shaped by melanoma expressing either a low-avidity tumor-associated antigen or high-avidity neoantigen, and kinetically profiled T cell differentiation in these two contexts across host tissues. High-avidity neoantigen expression was sufficient to activate na\u00efve CD8+ T cells &#8211; leading to robust tumor regression and long-term protective immunity upon tumor rechallenge. Mechanistically, transferred na\u00efve CD8+ T cells reacting to high-avidity neoantigen exhibited enhanced cytokine production, heightened effector function, and sustained persistence compared to the low-avidity wild-type tumors. Antitumor activity to these high-avidity tumors was preserved even in the absence of functional host T and B lymphocytes, and early lymph node trafficking was found to be essential for ACT efficacy. Expanded effector or stem-memory T cells were compared to the na\u00efve pmel-1 T cell product. Stem-memory but not effector-memory cells exhibited similar antitumor efficacy and lymph node trafficking patterns to the na\u00efve cells in mice with high-avidity neoantigen tumors. These findings highlight how differential tumor antigens shape divergent cellular fate and uncover a critical role of T cell trafficking in lymph nodes in shaping high-avidity neoantigen-specific antitumor responses.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41348132\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20251205144402&amp;v=2.18.0.post22+67771e2\">41348132<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-0514\">10.1158\/2326-6066.CIR-25-0514<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Dec 5. doi: 10.1158\/2326-6066.CIR-25-0514. Online ahead of print. ABSTRACT Adoptive transfer of T lymphocytes specific for tumor-associated neoantigens can elicit immunity against solid tumors in patients. However, how these antigens impact T cell function, effector differentiation, and persistence remains unclear. We examined how an identical CD8+ T cell product was shaped &#8230; <a title=\"T cell priming by high avidity neoantigens in lymph nodes augments adoptive immunotherapy\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/12\/05\/t-cell-priming-by-high-avidity-neoantigens-in-lymph-nodes-augments-adoptive-immunotherapy\/\" aria-label=\"Read more about T cell priming by high avidity neoantigens in lymph nodes augments adoptive immunotherapy\">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-50083","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\/50083","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=50083"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/50083\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=50083"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=50083"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=50083"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}