Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors

Bertrand Routy 1, 2, 3 Emmanuelle Le Chatelier 4 Lisa Derosa 1, 2, 3 Connie P. M. Duong 1, 2, 5 Maryam Tidjani Alou 1, 2, 3 Romain Daillère 1, 2, 3 Aurélie Fluckiger 1, 2, 5 Meriem Messaoudene 1, 2 Conrad Rauber 1, 2, 3 Maria P. Roberti 1, 2, 5 Marine Fidelle 1, 5 Caroline Flament 1, 2, 5 Vichnou Poirier-Colame 1, 2, 5 Paule Opolon 6 Christophe Klein Kristina Iribarren Laura Mondragón Nicolas Jacquelot Bo Qu Gladys Ferrere Céline Clémenson Laura Mezquita 7 Jordi Remon Masip 7 Charles Naltet Solenn Brosseau Coureche Kaderbhai 8 Corentin Richard 8 Hira Rizvi Florence Levenez Nathalie Galleron Benoit Quinquis Nicolas Pons Bernhard Ryffel Véronique Minard-Colin 9 Patrick Gonin Jean-Charles Soria 7 Eric Deutsch 10, 11 Yohann Loriot 12 François Ghiringhelli 8 Gérard Zalcman François Goldwasser Bernard Escudier 12 Matthew D. Hellmann Alexander Eggermont 1 Didier Raoult Laurence Albiges 12 Guido Kroemer 13, 14, 15, * Laurence Zitvogel 5, 2, 1, *
Abstract : Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so. Metagenomics of patient stool samples at diagnosis revealed correlations between clinical responses to ICIs and the relative abundance of Akkermansia muciniphila. Oral supplementation with A. muciniphila after FMT with nonresponder feces restored the efficacy of PD-1 blockade in an interleukin-12–dependent manner by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into mouse tumor beds.
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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01727917
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : vendredi 9 mars 2018 - 16:22:40
Dernière modification le : mardi 28 mai 2019 - 01:48:01

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Bertrand Routy, Emmanuelle Le Chatelier, Lisa Derosa, Connie P. M. Duong, Maryam Tidjani Alou, et al.. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science, American Association for the Advancement of Science, 2018, 359 (6371), pp.91-97. ⟨http://science.sciencemag.org/content/359/6371/91.long⟩. ⟨10.1126/science.aan3706 ⟩. ⟨hal-01727917⟩

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