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Publication : A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers.

First Author  Fidelle M Year  2023
Journal  Science Volume  380
Issue  6649 Pages  eabo2296
PubMed ID  37289890 Mgi Jnum  J:337204
Mgi Id  MGI:7493535 Doi  10.1126/science.abo2296
Citation  Fidelle M, et al. (2023) A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers. Science 380(6649):eabo2296
abstractText  Antibiotics (ABX) compromise the efficacy of programmed cell death protein 1 (PD-1) blockade in cancer patients, but the mechanisms underlying their immunosuppressive effects remain unknown. By inducing the down-regulation of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in the ileum, post-ABX gut recolonization by Enterocloster species drove the emigration of enterotropic alpha4beta7(+)CD4(+) regulatory T 17 cells into the tumor. These deleterious ABX effects were mimicked by oral gavage of Enterocloster species, by genetic deficiency, or by antibody-mediated neutralization of MAdCAM-1 and its receptor, alpha4beta7 integrin. By contrast, fecal microbiota transplantation or interleukin-17A neutralization prevented ABX-induced immunosuppression. In independent lung, kidney, and bladder cancer patient cohorts, low serum levels of soluble MAdCAM-1 had a negative prognostic impact. Thus, the MAdCAM-1-alpha4beta7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance.
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