Медицинская библиотека · Science (New York, N.Y.) · 2017

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

Routy Bertrand, Le Chatelier Emmanuelle, Derosa Lisa, Duong Connie P M, Alou Maryam Tidjani, Daillère Romain, Fluckiger Aurélie, Messaoudene Meriem, Rauber Conrad, Roberti Maria P, Fidelle Marine, Flament Caroline, Poirier-Colame Vichnou, Opolon Paule, Klein Christophe, Iribarren Kristina, Mondragón Laura, Jacquelot Nicolas, Qu Bo, Ferrere Gladys, Clémenson Céline, Mezquita Laura, Masip Jordi Remon, Naltet Charles, Brosseau Solenn, Kaderbhai Coureche, Richard Corentin, Rizvi Hira, Levenez Florence, Galleron Nathalie, Quinquis Benoit, Pons Nicolas, Ryffel Bernhard, Minard-Colin Véronique, Gonin Patrick, Soria Jean-Charles, Deutsch Eric, Loriot Yohann, Ghiringhelli François, Zalcman Gérard, Goldwasser François, Escudier Bernard, Hellmann Matthew D, Eggermont Alexander, Raoult Didier, Albiges Laurence, Kroemer Guido, Zitvogel Laurence

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Аннотация

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.

Для цитирования: Routy Bertrand, Le Chatelier Emmanuelle, Derosa Lisa, Duong Connie P M, Alou Maryam Tidjani, Daillère Romain, Fluckiger Aurélie, Messaoudene Meriem, Rauber Conrad, Roberti Maria P, Fidelle Marine, Flament Caroline, Poirier-Colame Vichnou, Opolon Paule, Klein Christophe, Iribarren Kristina, Mondragón Laura, Jacquelot Nicolas, Qu Bo, Ferrere Gladys, Clémenson Céline, Mezquita Laura, Masip Jordi Remon, Naltet Charles, Brosseau Solenn, Kaderbhai Coureche, Richard Corentin, Rizvi Hira, Levenez Florence, Galleron Nathalie, Quinquis Benoit, Pons Nicolas, Ryffel Bernhard, Minard-Colin Véronique, Gonin Patrick, Soria Jean-Charles, Deutsch Eric, Loriot Yohann, Ghiringhelli François, Zalcman Gérard, Goldwasser François, Escudier Bernard, Hellmann Matthew D, Eggermont Alexander, Raoult Didier, Albiges Laurence, Kroemer Guido, Zitvogel Laurence. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors.. Science (New York, N.Y.). 2017. DOI: 10.1126/science.aan3706.

Предметные рубрики MeSH

Animals Anti-Bacterial Agents Antibodies, Monoclonal CD4 Antigens Fecal Microbiota Transplantation Feces Gastrointestinal Microbiome Humans Immunotherapy Interleukin-12 Metagenome Mice Neoplasms Programmed Cell Death 1 Receptor Receptors, CCR Receptors, CXCR3 T-Lymphocytes Verrucomicrobia

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