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

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

doi:10.1126/science.abo2296

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

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

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

50 Citations (Scopus)

Résumé

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 a4b7⁺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, a4b7 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–a4b7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance.

langue originale	Anglais
Numéro d'article	eabo2296
journal	Science
Volume	380
Numéro de publication	6649
Les DOIs	https://doi.org/10.1126/science.abo2296
état	Publié - 9 juin 2023
Modification externe	Oui

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10.1126/science.abo2296

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Fidelle, M., Rauber, C., Silva, C. A. C., Tian, A. L., Lahmar, I., de La Varende, A. L. M., Zhao, L., Thelemaque, C., Lebhar, I., Messaoudene, M., Pizzato, E., Birebent, R., Fonkou, M. D. M., Zoppi, S., Reni, A., Dalban, C., Leduc, M., Ferrere, G., Durand, S., ... Zitvogel, L. (2023). A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers. Science, 380(6649), Article eabo2296. https://doi.org/10.1126/science.abo2296

@article{35fadd995749434698bd72c42342c36f,

title = "A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers",

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 a4b7+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, a4b7 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–a4b7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance.",

author = "Marine Fidelle and Conrad Rauber and Silva, {Carolina Alves Costa} and Tian, {Ai Ling} and Imran Lahmar and {de La Varende}, {Anne Laure Mallard} and Liwei Zhao and Cassandra Thelemaque and Isabelle Lebhar and Meriem Messaoudene and Eugenie Pizzato and Roxanne Birebent and Fonkou, {Maxime Descartes Mbogning} and Silvia Zoppi and Anna Reni and C{\'e}cile Dalban and Marion Leduc and Gladys Ferrere and Sylv{\`e}re Durand and Pierre Ly and Aymeric Silvin and Kevin Mulder and Dutertre, {Charles Antoine} and Florent Ginhoux and Satoru Yonekura and Roberti, {Maria Paula} and Maryam Tidjani-Alou and Safae Terrisse and Jianzhou Chen and Oliver Kepp and Angela Schippers and Norbert Wagner and Javier Su{\'a}rez-Gos{\'a}lvez and Sebastian Kobold and Fahrner, {Jean Eudes} and Corentin Richard and Jacques Bosq and Leonardo Lordello and Giacomo Vitali and Nathalie Galleron and Beno{\^i}t Quinquis and {Le Chatelier}, Emmanuelle and Lucas Blanchard and Girard, {Jean Philippe} and Anne Jarry and Nadine Gervois and Emmanuelle Godefroy and Nathalie Labarri{\`e}re and Ronald Koschny and Romain Daill{\`e}re and Benjamin Besse and Caroline Truntzer and Fran{\c c}ois Ghiringhelli and Nicolas Coatnoan and Vanessa Mhanna and David Klatzmann and Damien Drubay and Laurence Albiges and Thomas, {Andrew Maltez} and Nicola Segata and Danlos, {Fran{\c c}ois Xavier} and Aur{\'e}lien Marabelle and Bertrand Routy and Lisa Derosa and Guido Kroemer and Laurence Zitvogel",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 the authors, some rights reserved.",

year = "2023",

month = jun,

day = "9",

doi = "10.1126/science.abo2296",

language = "English",

volume = "380",

journal = "Science",

issn = "0036-8075",

number = "6649",

}

Fidelle, M, Rauber, C, Silva, CAC, Tian, AL, Lahmar, I, de La Varende, ALM, Zhao, L, Thelemaque, C, Lebhar, I, Messaoudene, M, Pizzato, E, Birebent, R, Fonkou, MDM, Zoppi, S, Reni, A, Dalban, C, Leduc, M, Ferrere, G, Durand, S, Ly, P, Silvin, A, Mulder, K, Dutertre, CA, Ginhoux, F, Yonekura, S, Roberti, MP, Tidjani-Alou, M, Terrisse, S, Chen, J, Kepp, O, Schippers, A, Wagner, N, Suárez-Gosálvez, J, Kobold, S, Fahrner, JE, Richard, C, Bosq, J, Lordello, L, Vitali, G, Galleron, N, Quinquis, B, Le Chatelier, E, Blanchard, L, Girard, JP, Jarry, A, Gervois, N, Godefroy, E, Labarrière, N, Koschny, R, Daillère, R, Besse, B, Truntzer, C, Ghiringhelli, F, Coatnoan, N, Mhanna, V, Klatzmann, D, Drubay, D, Albiges, L, Thomas, AM, Segata, N, Danlos, FX, Marabelle, A, Routy, B, Derosa, L, Kroemer, G & Zitvogel, L 2023, 'A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers', Science, VOL. 380, Numéro 6649, eabo2296. https://doi.org/10.1126/science.abo2296

TY - JOUR

T1 - A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers

AU - Fidelle, Marine

AU - Rauber, Conrad

AU - Silva, Carolina Alves Costa

AU - Tian, Ai Ling

AU - Lahmar, Imran

AU - de La Varende, Anne Laure Mallard

AU - Zhao, Liwei

AU - Thelemaque, Cassandra

AU - Lebhar, Isabelle

AU - Messaoudene, Meriem

AU - Pizzato, Eugenie

AU - Birebent, Roxanne

AU - Fonkou, Maxime Descartes Mbogning

AU - Zoppi, Silvia

AU - Reni, Anna

AU - Dalban, Cécile

AU - Leduc, Marion

AU - Ferrere, Gladys

AU - Durand, Sylvère

AU - Ly, Pierre

AU - Silvin, Aymeric

AU - Mulder, Kevin

AU - Dutertre, Charles Antoine

AU - Ginhoux, Florent

AU - Yonekura, Satoru

AU - Roberti, Maria Paula

AU - Tidjani-Alou, Maryam

AU - Terrisse, Safae

AU - Chen, Jianzhou

AU - Kepp, Oliver

AU - Schippers, Angela

AU - Wagner, Norbert

AU - Suárez-Gosálvez, Javier

AU - Kobold, Sebastian

AU - Fahrner, Jean Eudes

AU - Richard, Corentin

AU - Bosq, Jacques

AU - Lordello, Leonardo

AU - Vitali, Giacomo

AU - Galleron, Nathalie

AU - Quinquis, Benoît

AU - Le Chatelier, Emmanuelle

AU - Blanchard, Lucas

AU - Girard, Jean Philippe

AU - Jarry, Anne

AU - Gervois, Nadine

AU - Godefroy, Emmanuelle

AU - Labarrière, Nathalie

AU - Koschny, Ronald

AU - Daillère, Romain

AU - Besse, Benjamin

AU - Truntzer, Caroline

AU - Ghiringhelli, François

AU - Coatnoan, Nicolas

AU - Mhanna, Vanessa

AU - Klatzmann, David

AU - Drubay, Damien

AU - Albiges, Laurence

AU - Thomas, Andrew Maltez

AU - Segata, Nicola

AU - Danlos, François Xavier

AU - Marabelle, Aurélien

AU - Routy, Bertrand

AU - Derosa, Lisa

AU - Kroemer, Guido

AU - Zitvogel, Laurence

PY - 2023/6/9

Y1 - 2023/6/9

N2 - 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 a4b7+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, a4b7 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–a4b7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance.

AB - 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 a4b7+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, a4b7 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–a4b7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance.

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U2 - 10.1126/science.abo2296

DO - 10.1126/science.abo2296

M3 - Article

C2 - 37289890

AN - SCOPUS:85161983442

SN - 0036-8075

VL - 380

JO - Science

JF - Science

IS - 6649

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ER -