{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:57:02Z","timestamp":1785401822163,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,18]]},"group-title":"Immunology","reference-count":37,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["AI150214"],"award-info":[{"award-number":["AI150214"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["AI176333"],"award-info":[{"award-number":["AI176333"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Interferon regulatory factor 1 (IRF1) has long been recognized as a tumor suppressor; however, recent studies have revealed context-specific and sometimes opposing roles in cancer progression. Here, we describe a T cell\u2013specific mechanism underlying the antitumor activity of IRF1. Unlike germline\n                  <jats:italic>Irf1<\/jats:italic>\n                  -deficient mice, T cell\u2013specific loss of IRF1 does not lead to a deficiency in cytotoxic CD8\u207a T cells. Nevertheless, tumor burden remains elevated in these mice, associated with reduced CD8\u207a T cell infiltration driven by impaired activation and proliferation in the absence of IRF1. Transcriptomic analysis of activated\n                  <jats:italic>Irf1<\/jats:italic>\n                  -deficient T cells identified NFATc1 as a key gene significantly downregulated upon IRF1 loss. Analysis of human melanoma datasets further corroborated this finding, highlighting a previously unappreciated role for IRF1 in regulating T cell activation and antitumor immunity.\n                <\/jats:p>","DOI":"10.64898\/2026.05.14.725206","type":"posted-content","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:05:16Z","timestamp":1779134716000},"source":"Crossref","is-referenced-by-count":0,"title":["T cell-specific loss of IRF1 results in defective CD8 T cell activation and antitumor immunity"],"prefix":"10.64898","author":[{"given":"Lulu","family":"Shao","sequence":"first","affiliation":[{"name":"Cancer Virology Program, University of Pittsburgh Cancer Institute"},{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hridesh","family":"Bannerjee","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Pittsburgh School of Medicine, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ecem","family":"Unal","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isha","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Pittsburgh School of Medicine, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5747-064X","authenticated-orcid":false,"given":"Jishnu","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Pittsburgh School of Medicine, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Rouf","family":"Banday","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5198-516X","authenticated-orcid":false,"given":"Larry","family":"Kane","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Pittsburgh School of Medicine, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2850-6121","authenticated-orcid":false,"given":"Saumendra N.","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Cancer Virology Program, University of Pittsburgh Cancer Institute"},{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA"},{"name":"Department of Immunology University of Pittsburgh School of Medicine, Pittsburgh, PA"},{"name":"Program in Oncology, Marlene & Stewart Greenebaum Comprehensive Cancer Center and Dept. of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052101501567000_2026.05.14.725206v1.1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.623"},{"key":"2026052101501567000_2026.05.14.725206v1.2","doi-asserted-by":"publisher","DOI":"10.1006\/scbi.2000.0310"},{"key":"2026052101501567000_2026.05.14.725206v1.3","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028423"},{"key":"2026052101501567000_2026.05.14.725206v1.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.8438156"},{"key":"2026052101501567000_2026.05.14.725206v1.5","doi-asserted-by":"crossref","first-page":"BSR20171672","DOI":"10.1042\/BSR20171672","article-title":"Interferon regulatory factor 1 inactivation in human cancer","volume":"38","year":"2018","journal-title":"Bioscience Reports. 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