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

• DOI: 10.1126/science.aan3706
• Publication Date: 2017-11-02T18:12:28Z
• Authors: Bertrand Routy; Emmanuelle Le Cha...; Lisa Derosa; Connie P. M. Duong; Maryam Tidjani Alou; Romain Daillère; Aurélie Fluckiger; Meriem Messaoudene; Conrad Rauber; Maria P. Roberti; Marine Fidelle; Caroline Flament; Vichnou Poirier-C...; Paule Opolon; Christophe Klein; Kristina Iribarren; Laura Mondragón; Nicolas Jacquelot; Bo Qu; Gladys Ferrere; Céline Clémenson; Laura Mezquita; Jordi Remon Masip; Charles Naltet; Solenn Brosseau; Coureche Kaderbhai; Corentin Richard; Hira Rizvi; Florence Levenez; Nathalie Galleron; Benoit Quinquis; Nicolas Pons; Bernhard Ryffel; Véronique Minard-...; Patrick Gonin; Jean-Charles Soria; Eric Deutsch; Yohann Loriot; François Ghiringh...; Gérard Zalcman; François Goldwasser; Bernard Escudier; Matthew D. Hellmann; Alexander Eggermont; Didier Raoult; Laurence Albiges; Guido Kroemer; Laurence Zitvogel
• Keywords: Akkermansia muciniphila; CXCR3; Fecal bacteriotherapy

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 abnormal gut microbiome composition. Antibiotics inhibited benefit patients with advanced cancer. Fecal microbiota transplantation (FMT) from who responded into germ-free or antibiotic-treated mice ameliorated antitumor effects PD-1 blockade, whereas FMT nonresponding failed do so. Metagenomics patient stool samples at diagnosis revealed correlations between and relative abundance Akkermansia muciniphila Oral supplementation A. after nonresponder feces restored efficacy blockade an interleukin-12-dependent manner by increasing recruitment CCR9+CXCR3+CD4+ T lymphocytes mouse tumor beds.