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In contrast, abundance of colonic T-IELs was dependent on the microbiome and displayed higher expression of TCF-1\/\n            <jats:italic>TCF7<\/jats:italic>\n            and a reduced effector and cytotoxic profile, including low expression of granzymes. Targeted deletion of TCF-1 in \u03b3\u03b4 T-IELs induced a distinct effector profile and reduced colon tumor formation in mice. In addition, TCF-1 expression was significantly reduced in \u03b3\u03b4 T-IELs present in human colorectal cancers (CRCs) compared with normal healthy colon, which strongly correlated with an enhanced \u03b3\u03b4 T-IEL effector phenotype and improved patient survival. Our work identifies TCF-1 as a colon-specific T-IEL transcriptional regulator that could inform new immunotherapy strategies to treat CRC.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.adf2163","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T17:57:41Z","timestamp":1696615061000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":31,"title":["TCF-1 limits intraepithelial lymphocyte antitumor immunity in colorectal carcinoma"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4618-4118","authenticated-orcid":true,"given":"Marina H.","family":"Yakou","sequence":"first","affiliation":[{"name":"Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, 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