{"id":49120,"date":"2025-11-19T12:49:52","date_gmt":"2025-11-19T11:49:52","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/11\/19\/il-15-complex-enhances-therapeutic-efficacy-of-anti-pd-l1-in-a-t-cell-dependent-and-nk-cell-independent-manner-in-a-murine-model-of-pancreatic-ductal-adenocarcinoma\/"},"modified":"2025-11-19T12:49:52","modified_gmt":"2025-11-19T11:49:52","slug":"il-15-complex-enhances-therapeutic-efficacy-of-anti-pd-l1-in-a-t-cell-dependent-and-nk-cell-independent-manner-in-a-murine-model-of-pancreatic-ductal-adenocarcinoma","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/11\/19\/il-15-complex-enhances-therapeutic-efficacy-of-anti-pd-l1-in-a-t-cell-dependent-and-nk-cell-independent-manner-in-a-murine-model-of-pancreatic-ductal-adenocarcinoma\/","title":{"rendered":"IL-15 complex enhances therapeutic efficacy of anti-PD-L1 in a T cell-dependent and NK cell-independent manner in a murine model of pancreatic ductal adenocarcinoma"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Nov 18:vkaf314. doi: 10.1093\/jimmun\/vkaf314. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy resistant to therapy including immune checkpoint blockade (ICB). We previously showed that ICB selects for pancreatic tumor cells that are defective in IFN-\u03b3-inducible MHC-I, prompting us to test the impact of IL-15 complex (IL-15C) in overcoming ICB resistance. Here, we show that IL-15C markedly expands circulating NK cells, CD8+ T cells, and CD4+Cxcr3+ T cells in an orthotopic pancreatic ductal adenocarcinoma (PDA) animal model. In tumors, IL-15C + anti-PD-L1 increased CD8+ T-cell effector cytokine production and interfered with T-cell exhaustion, including mitigating IL-10. In NK cells, IL-15C + anti-PD-L1 modulated NK cell IFN-\u03b3 production but did not alter Nkg2d, Nkg2a, Klrg1, IL-10, or granzyme B. IL-15C + anti-PD-L1 significantly prolonged animal survival, leading to tumor eradication in a subset of animals, whereas monotherapies only transiently prolonged survival. Therapeutic benefit was dependent on CD8+ T cells and independent of NK cells and Nkg2d. Together, our study supports that IL-15C improves anti-PD-L1 in PDA through sustaining antitumor T-cell function.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41254945\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20251119064951&amp;v=2.18.0.post22+67771e2\">41254945<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf314\">10.1093\/jimmun\/vkaf314<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Nov 18:vkaf314. doi: 10.1093\/jimmun\/vkaf314. Online ahead of print. ABSTRACT Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy resistant to therapy including immune checkpoint blockade (ICB). We previously showed that ICB selects for pancreatic tumor cells that are defective in IFN-\u03b3-inducible MHC-I, prompting us to test the impact of IL-15 complex (IL-15C) in &#8230; <a title=\"IL-15 complex enhances therapeutic efficacy of anti-PD-L1 in a T cell-dependent and NK cell-independent manner in a murine model of pancreatic ductal adenocarcinoma\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/11\/19\/il-15-complex-enhances-therapeutic-efficacy-of-anti-pd-l1-in-a-t-cell-dependent-and-nk-cell-independent-manner-in-a-murine-model-of-pancreatic-ductal-adenocarcinoma\/\" aria-label=\"Read more about IL-15 complex enhances therapeutic efficacy of anti-PD-L1 in a T cell-dependent and NK cell-independent manner in a murine model of pancreatic ductal adenocarcinoma\">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":[42,71],"tags":[],"class_list":["post-49120","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/49120","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=49120"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/49120\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=49120"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=49120"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=49120"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}