Science (New York, N.Y.) · 2023

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

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

Аннотация

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.

Предметные рубрики MeSH

Animals Humans Mice Anti-Bacterial Agents Bacteria Cell Adhesion Molecules Cell Movement Drug Resistance, Neoplasm Fecal Microbiota Transplantation Gastrointestinal Microbiome Immune Checkpoint Inhibitors Immune Tolerance Immunologic Surveillance Integrins Interleukin-17 Mucoproteins Neoplasms Th17 Cells Gastrointestinal Tract

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

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH