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