Science immunology · 2023
TCF-1 limits intraepithelial lymphocyte antitumor immunity in colorectal carcinoma.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Yakou Marina H, Ghilas Sonia, Tran Kelly, Liao Yang, Afshar-Sterle Shoukat, Kumari Anita, Schmid Kevin, Dijkstra Christine, Inguanti Chantelle, Ostrouska Simone, Wilcox Jordan, Smith Maxine, Parathan Pavitha, Allam Amr, Xue Hai-Hui, Belz Gabrielle T, Mariadason John M, Behren Andreas, Drummond Grant R, Ruscher Roland, Williams David S, Pal Bhupinder, Shi Wei, Ernst Matthias, Raghu Dinesh, Mielke Lisa A
Аннотация
Intraepithelial lymphocytes (IELs), including αβ and γδ T cells (T-IELs), constantly survey and play a critical role in maintaining the gastrointestinal epithelium. We show that cytotoxic molecules important for defense against cancer were highly expressed by T-IELs in the small intestine. In contrast, abundance of colonic T-IELs was dependent on the microbiome and displayed higher expression of TCF-1/TCF7 and a reduced effector and cytotoxic profile, including low expression of granzymes. Targeted deletion of TCF-1 in γδ T-IELs induced a distinct effector profile and reduced colon tumor formation in mice. In addition, TCF-1 expression was significantly reduced in γδ T-IELs present in human colorectal cancers (CRCs) compared with normal healthy colon, which strongly correlated with an enhanced γδ 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.