A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers.
Science
; 380(6649): eabo2296, 2023 06 09.
Article
in En
| MEDLINE
| ID: mdl-37289890
ABSTRACT
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 α4ß7+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, α4ß7 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-α4ß7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Adhesion Molecules
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Integrins
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Drug Resistance, Neoplasm
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Gastrointestinal Microbiome
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Immune Checkpoint Inhibitors
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Immune Tolerance
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Immunologic Surveillance
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Anti-Bacterial Agents
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Mucoproteins
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Neoplasms
Limits:
Animals
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Humans
Language:
En
Journal:
Science
Year:
2023
Document type:
Article
Affiliation country: