TCF-1 limits intraepithelial lymphocyte antitumor immunity in colorectal carcinoma.

Autor:	Yakou MH; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Ghilas S; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Tran K; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Liao Y; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Afshar-Sterle S; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Kumari A; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Schmid K; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Dijkstra C; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Inguanti C; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Ostrouska S; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Wilcox J; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Smith M; Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia., Parathan P; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Allam A; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Xue HH; Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, NJ, USA.; New Jersey Veterans Affairs Health Care System, East Orange, NJ, USA., Belz GT; University of Queensland Frazer Institute, Faculty of Medicine, University of Queensland, Woolloongabba, Queensland 4102, Australia., Mariadason JM; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Behren A; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Drummond GR; Centre for Cardiovascular Biology and Disease Research; Department of Microbiology, Anatomy, Physiology and Pharmacology; and School of Agriculture, Biomedicine, and Environment, La Trobe University, Bundoora, Victoria, Australia., Ruscher R; Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia., Williams DS; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia.; Department of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia., Pal B; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Shi W; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Ernst M; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Raghu D; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia., Mielke LA; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria 3084, Australia.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2023 Oct 13; Vol. 8 (88), pp. eadf2163. Date of Electronic Publication: 2023 Oct 06.
DOI:	10.1126/sciimmunol.adf2163
Abstrakt:	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.
Databáze:	MEDLINE
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