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

Date publication

janvier 2018

Journal

Science (New York, N.Y.)

Auteurs

Membres identifiés du Cancéropôle Est :
Pr GHIRINGHELLI François

Tous les auteurs :
Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, Fidelle M, Flament C, Poirier-Colame V, Opolon P, Klein C, Iribarren K, Mondragón L, Jacquelot N, Qu B, Ferrere G, Clémenson C, Mezquita L, Masip JR, Naltet C, Brosseau S, Kaderbhai C, Richard C, Rizvi H, Levenez F, Galleron N, Quinquis B, Pons N, Ryffel B, Minard-Colin V, Gonin P, Soria JC, Deutsch E, Loriot Y, Ghiringhelli F, Zalcman G, Goldwasser F, Escudier B, Hellmann MD, Eggermont A, Raoult D, Albiges L, Kroemer G, Zitvogel L

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/29097494

Résumé

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 Oral supplementation with after FMT with nonresponder feces restored the efficacy of PD-1 blockade in an interleukin-12-dependent manner by increasing the recruitment of CCR9CXCR3CD4 T lymphocytes into mouse tumor beds.

Mots clés

Animals, Anti-Bacterial Agents, therapeutic use, Antibodies, Monoclonal, therapeutic use, CD4 Antigens, immunology, Fecal Microbiota Transplantation, Feces, microbiology, Gastrointestinal Microbiome, genetics, Humans, Immunotherapy, methods, Interleukin-12, immunology, Metagenome, genetics, Mice, Neoplasms, therapy, Programmed Cell Death 1 Receptor, antagonists & inhibitors, Receptors, CCR, immunology, Receptors, CXCR3, immunology, T-Lymphocytes, immunology, Verrucomicrobia, genetics

Référence

Science. 2018 Jan 5;359(6371):91-97