{"id":16855,"date":"2024-09-29T09:29:35","date_gmt":"2024-09-29T07:29:35","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/hyper-interferon-sensitive-influenza-induces-adaptive-immune-responses-and-overcomes-resistance-to-anti-pd-1-in-murine-non-small-cell-lung-cancer\/"},"modified":"2024-09-29T09:29:35","modified_gmt":"2024-09-29T07:29:35","slug":"hyper-interferon-sensitive-influenza-induces-adaptive-immune-responses-and-overcomes-resistance-to-anti-pd-1-in-murine-non-small-cell-lung-cancer","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/hyper-interferon-sensitive-influenza-induces-adaptive-immune-responses-and-overcomes-resistance-to-anti-pd-1-in-murine-non-small-cell-lung-cancer\/","title":{"rendered":"Hyper-Interferon Sensitive influenza induces adaptive immune responses and overcomes resistance to anti-PD-1 in murine non-small cell lung cancer"},"content":{"rendered":"<div>\n<p>Cancer Immunol Res. 2024 Sep 26. doi: 10.1158\/2326-6066.CIR-23-1075. Online ahead of print.<\/p>\n<p>ABSTRACT<\/p>\n<p>Despite recent advances in immunotherapy with immune checkpoint inhibitors (ICI), many patients with non-small cell lung cancer (NSCLC) fail to respond or develop resistance after an initial response. In situ vaccination (ISV) with engineered viruses has emerged as a promising antigen-agnostic strategy that can both condition the tumor microenvironment (TME) and augment anti-tumor T cell responses to overcome immune resistance. We engineered a live attenuated viral vaccine, Hyper-Interferon Sensitive virus (HIS), by conducting a genome-wide functional screening and introducing eight interferon (IFN)-sensitive mutations in the influenza genome. Compared to wild-type (WT) influenza, HIS replication was attenuated in immunocompetent hosts, enhancing its potential as a safe option for cancer therapy. HIS ISV elicited robust yet transient type I IFN responses in murine NSCLCs, leading to an enrichment of polyfunctional effector Th1 CD4 and cytotoxic CD8 T cells into the tumor. HIS ISV demonstrated enhanced anti-tumor efficacy compared to WT in multiple syngeneic murine models of NSCLC with distinct driver mutations and varying mutational burden. This efficacy was dependent on host type 1 IFN responses and T lymphocytes. HIS ISV overcame resistance to anti-PD-1 in LKB-1 deficient murine NSCLC, resulting in improved overall survival and enduring systemic tumor-specific immunity. These studies provide compelling evidence to support further clinical evaluation of HIS as a novel &#8216;off-the-shelf&#8217; ISV strategy for patients with NSCLC refractory to ICI.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39325056\/?utm_source=Chrome&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20240929032735&amp;v=2.18.0.post9+e462414\">39325056<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-23-1075\">10.1158\/2326-6066.CIR-23-1075<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2024 Sep 26. doi: 10.1158\/2326-6066.CIR-23-1075. Online ahead of print. ABSTRACT Despite recent advances in immunotherapy with immune checkpoint inhibitors (ICI), many patients with non-small cell lung cancer (NSCLC) fail to respond or develop resistance after an initial response. In situ vaccination (ISV) with engineered viruses has emerged as a promising antigen-agnostic strategy &#8230; <a title=\"Hyper-Interferon Sensitive influenza induces adaptive immune responses and overcomes resistance to anti-PD-1 in murine non-small cell lung cancer\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/hyper-interferon-sensitive-influenza-induces-adaptive-immune-responses-and-overcomes-resistance-to-anti-pd-1-in-murine-non-small-cell-lung-cancer\/\" aria-label=\"Read more about Hyper-Interferon Sensitive influenza induces adaptive immune responses and overcomes resistance to anti-PD-1 in murine non-small cell lung 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-16855","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\/16855","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=16855"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/16855\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=16855"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=16855"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=16855"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}