{"id":63823,"date":"2026-05-11T19:47:26","date_gmt":"2026-05-11T17:47:26","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/05\/11\/low-strength-type-i-interferon-signaling-promotes-car-t-cell-treatment-efficacy\/"},"modified":"2026-05-11T19:47:26","modified_gmt":"2026-05-11T17:47:26","slug":"low-strength-type-i-interferon-signaling-promotes-car-t-cell-treatment-efficacy","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/05\/11\/low-strength-type-i-interferon-signaling-promotes-car-t-cell-treatment-efficacy\/","title":{"rendered":"Low-Strength Type I Interferon Signaling Promotes CAR T Cell Treatment Efficacy"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 May 11. doi: 10.1158\/2326-6066.CIR-25-0691. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>CD19-directed chimeric antigen receptor (CAR) T-cell therapy has significantly advanced the treatment landscape for relapsed\/refractory diffuse large B-cell lymphoma (r\/r DLBCL). However, up to 60% of patients do not achieve a complete response. To uncover determinants of therapeutic efficacy, we analyzed the infusion products of eight r\/r DLBCL patients with distinct clinical responses to axicabtagene ciloleucel using single-cell transcriptomics. Compared to patients who exhibited progressive disease, infusion products of complete responders demonstrated enriched signatures of type I interferon (IFN-I) signaling. Based on these findings, we developed a novel strategy to improve CD19-directed CAR T-cell treatment efficacy by incorporating IFN-I as an enhancer during the ex vivo manufacturing process, with IFN-I removal before CAR T-cell infusion to avoid in vivo toxicities. For both CD28- and 4-1BB-costimulated second-generation CARs, we found that low-strength IFN-I signaling enhanced CAR T-cell cytotoxicity and treatment efficacy against B-cell lymphoma and leukemia. Our low-strength IFN-I-enhanced CAR T-cell ex vivo manufacturing approach leverages an existing FDA-approved pharmacologic agent, circumvents in vivo interferon-associated toxicities, and remains fully compatible with current CAR constructs and manufacturing workflows. Together, our results establish IFN-I as a potent and costimulation-independent enhancer of CAR T-cell efficacy and provide a translationally feasible approach to enhance CAR T-cell therapies.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42112708\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260511134725&amp;v=2.20.0\">42112708<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-0691\">10.1158\/2326-6066.CIR-25-0691<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 May 11. doi: 10.1158\/2326-6066.CIR-25-0691. Online ahead of print. ABSTRACT CD19-directed chimeric antigen receptor (CAR) T-cell therapy has significantly advanced the treatment landscape for relapsed\/refractory diffuse large B-cell lymphoma (r\/r DLBCL). However, up to 60% of patients do not achieve a complete response. To uncover determinants of therapeutic efficacy, we analyzed the &#8230; <a title=\"Low-Strength Type I Interferon Signaling Promotes CAR T Cell Treatment Efficacy\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/05\/11\/low-strength-type-i-interferon-signaling-promotes-car-t-cell-treatment-efficacy\/\" aria-label=\"Read more about Low-Strength Type I Interferon Signaling Promotes CAR T Cell Treatment Efficacy\">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-63823","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\/63823","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=63823"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/63823\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=63823"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=63823"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=63823"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}