{"id":28234,"date":"2025-03-27T18:49:50","date_gmt":"2025-03-27T17:49:50","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/03\/27\/anti-ctla4-therapy-leads-to-early-expansion-of-a-peripheral-th17-population-and-induction-of-th1-cytokines\/"},"modified":"2025-03-27T18:49:50","modified_gmt":"2025-03-27T17:49:50","slug":"anti-ctla4-therapy-leads-to-early-expansion-of-a-peripheral-th17-population-and-induction-of-th1-cytokines","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/03\/27\/anti-ctla4-therapy-leads-to-early-expansion-of-a-peripheral-th17-population-and-induction-of-th1-cytokines\/","title":{"rendered":"Anti-CTLA4 therapy leads to early expansion of a peripheral Th17 population and induction of Th1 cytokines"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Mar 27. doi: 10.1158\/2326-6066.CIR-24-1055. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>The systemic immunological effects of combining anti-CTLA4 therapy with PD-(L)1 blockade remain incompletely characterized, despite the widespread use of this combination in treating various solid tumors across multiple stages of disease. Herein, we investigated the additive impact of anti-CTLA4 on peripheral immune signatures in patients undergoing PD-(L)1 blockade, using blood samples from a cohort of patients receiving checkpoint inhibitor therapy for advanced solid tumors. We performed in-parallel analysis of peripheral blood mononuclear cells (PBMC) using Cytometry by Time-of-Flight (CyTOF) and plasma cytokines using Luminex immunoassay. Our study cohort included 104 patients, 54 who received anti-PD(L)1 alone and 50 who received anti-PD(L)1 in combination with anti-CTLA4. As compared to single-agent anti-PD(L)1, combination therapy was associated with a greater expansion of CD4+ T helper cell subsets, including Th17 (adjusted p=0.04) and regulatory T cells (Treg) (adjusted p=0.02), after multivariable and multiple testing adjustment. In patients receiving anti-CTLA4, examination of functional marker expression within the Th17 subset revealed an increase in expression of the Th1-related transcription factor TBET (p=0.003). Assessment of the peripheral cytokine signatures showed an increase in Th1-associated cytokines (p=0.002) in recipients of combination anti-PD(L)1 and anti-CTLA4, particularly the IFN\uf067-inducible cytokines MIG (adjusted p=0.05) and IP-10 (adjusted p=0.05). Our results confirm prior reports that anti-CTLA4 therapy is associated with augmentation of Th17 cell subsets, and they also show that anti-CTLA4 may reshape CD4+ T-cell responses through Th17-to-Th1 plasticity, revealing a potential mechanism for enhanced antitumor immunity with broader implications immune modulation in immunotherapy.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40145982\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250327134949&amp;v=2.18.0.post9+e462414\">40145982<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-1055\">10.1158\/2326-6066.CIR-24-1055<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Mar 27. doi: 10.1158\/2326-6066.CIR-24-1055. Online ahead of print. ABSTRACT The systemic immunological effects of combining anti-CTLA4 therapy with PD-(L)1 blockade remain incompletely characterized, despite the widespread use of this combination in treating various solid tumors across multiple stages of disease. Herein, we investigated the additive impact of anti-CTLA4 on peripheral immune &#8230; <a title=\"Anti-CTLA4 therapy leads to early expansion of a peripheral Th17 population and induction of Th1 cytokines\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/03\/27\/anti-ctla4-therapy-leads-to-early-expansion-of-a-peripheral-th17-population-and-induction-of-th1-cytokines\/\" aria-label=\"Read more about Anti-CTLA4 therapy leads to early expansion of a peripheral Th17 population and induction of Th1 cytokines\">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-28234","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\/28234","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=28234"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/28234\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=28234"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=28234"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=28234"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}