A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles Science Year : 2023

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

Marine Fidelle
Conrad Rauber
Carolina Alves Costa Silva
Ai-Ling Tian
Imran Lahmar
  • Function : Author
Liwei Zhao
  • Function : Author
Cassandra Thelemaque
  • Function : Author
Isabelle Lebhar
  • Function : Author
Meriem Messaoudene
  • Function : Author
Eugenie Pizzato
  • Function : Author
Roxanne Birebent
Maxime Descartes Mbogning Fonkou
Silvia Zoppi
Anna Reni
  • Function : Author
Cécile Dalban
  • Function : Author
Marion Leduc
Gladys Ferrere
Sylvère Durand
  • Function : Author
Pierre Ly
  • Function : Author
Aymeric Silvin
Kevin Mulder
Charles-Antoine Dutertre
Florent Ginhoux
Satoru Yonekura
Maria Paula Roberti
Maryam Tidjani-Alou
Safae Terrisse
  • Function : Author
Jianzhou Chen
Oliver Kepp
Angela Schippers
Norbert Wagner
  • Function : Author
Javier Suárez-Gosálvez
Sebastian Kobold
Jean-Eudes Fahrner
Corentin Richard
  • Function : Author
Jacques Bosq
Leonardo Lordello
  • Function : Author
Giacomo Vitali
  • Function : Author
Nathalie Galleron
Benoît Quinquis
Lucas Blanchard
Jean-Philippe Girard
Anne Jarry
Nadine Gervois
Emmanuelle Godefroy
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
Laurence Albiges
Andrew Maltez Thomas
Nicola Segata
François-Xavier Danlos
Aurélien Marabelle
Bertrand Routy
  • Function : Author
Lisa Derosa
Guido Kroemer
Laurence Zitvogel

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.
No file

Dates and versions

hal-04143545 , version 1 (27-06-2023)

Identifiers

Cite

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. Science, 2023, 380 (6649), ⟨10.1126/science.abo2296⟩. ⟨hal-04143545⟩
1 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More