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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; [...]

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

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  • Medientyp: E-Artikel
  • Titel: A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers
  • Beteiligte: 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; [...]
  • Erschienen: American Association for the Advancement of Science (AAAS), 2023
  • Erschienen in: Science, 380 (2023) 6649
  • Sprache: Englisch
  • DOI: 10.1126/science.abo2296
  • ISSN: 0036-8075; 1095-9203
  • Entstehung:
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  • Beschreibung: 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.