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Preprints, Working Papers, ... (Preprint) Year : 2023

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

Ai-Ling Tian
Liwei Zhao
  • Function : Author
Meriem Messaoudene
  • Function : Author
Silvia Zoppi
Anna Reni
  • Function : Author
Cécile Dalban
  • Function : Author
Marion Leduc
Sylvère Durand
  • Function : Author
Oliver Kepp
Angela Schippers
Norbert Wagner
  • Function : Author
Javier Suárez-Gosálvez
Sebastian Kobold
Corentin Richard
  • Function : Author
Jacques Bosq
Giacomo Vitali
  • Function : Author
Nathalie Galleron
Benoît Quinquis
Emmanuelle Le Chatelier
Lucas Blanchard
Jean-Philippe Girard
Anne Jarry
Nadine Gervois
Nathalie Labarrière
Ronald Koschny
  • Function : Author
Romain Daillère
Benjamin Besse
Caroline Truntzer
François Ghiringhelli
  • Function : Author
Nicolas Coatnoan
  • Function : Author
Vanessa Mhanna
  • Function : Author
David Klatzmann
Damien Drubay
  • Function : Author
Andrew Maltez Thomas
Nicola Segata
Bertrand Routy
  • Function : Author

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 α4β7 + 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, α4β7 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–α4β7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance.
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hal-04597851 , version 1 (03-06-2024)

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Marine Fidelle, Conrad Rauber, Carolina Alves Costa Silva, Ai-Ling Tian, Imran Lahmar, et al.. A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers. 2024. ⟨hal-04597851⟩
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