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

Bertrand Routy 1 Emmanuelle Le Chatelier 2 Lisa Derosa 3 Connie Duong 1 Maryam Tidjani Alou 4, 1 Romain Daillère 1 Aurélie Fluckiger 3 Meriem Messaoudene 5 Conrad Rauber 3 Maria Roberti Marine Fidelle 3 Caroline Flament 6 Vichnou Poirier-Colame 3 Paule Opolon 3 Christophe Klein 7, 8, 9 Kristina Iribarren 7, 8, 10 Laura Mondragón 7, 8, 10 Nicolas Jacquelot 1 Bo Qu 11 Gladys Ferrere 12 Céline Clemenson 13 Laura Mezquita 14 Jordi Remon Masip 14 Charles Naltet Solenn Brosseau 15 Coureche Kaderbhai 16 Corentin Richard 17 Hira Rizvi Florence F. Levenez Nathalie Galleron Benoit Qu Nicolas Pons 18 Bernhard Ryffel 19 Véronique Minard-Colin 20 Patrick Gonin 3 Charles Soria Eric Deutsch 21, 22 Yohann Loriot 23, 24 François Ghiringhelli 16 Gérard Zalcman 25 François Goldwasser 26 Bernard Escudier 24 Matthew Hellmann Alexander M Eggermont 3 Didier Raoult 27 Laurence Albiges 24 Guido Kroemer 28, 29, 30, 8, 7, 10 Laurence Zitvogel 1, 31 
14 Oncologie thoracique
Département de médecine oncologique [Gustave Roussy]
17 Plateforme de transfert en biologie cancérologique [Dijon]
CEP - Centre d'épidémiologie des populations, UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
24 Oncologie génito-urinaire
Département de médecine oncologique [Gustave Roussy]
28 Plateforme de métabolomique
Direction de la recherche [Gustave Roussy]
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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Submitted on : Saturday, May 11, 2019 - 5:49:10 PM
Last modification on : Friday, September 23, 2022 - 10:44:04 AM



Bertrand Routy, Emmanuelle Le Chatelier, Lisa Derosa, Connie 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 (AAAS), 2018, 359 (6371), pp.91-97. ⟨10.1126/science.aan3706⟩. ⟨hal-02126484⟩



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