Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota
Marie VétizouINSERM U1015, GRCC, Villejuif, FranceJonathan M. PittINSERM U1015, GRCC, Villejuif, FranceRomain DaillèreINSERM U1015, GRCC, Villejuif, FrancePatricia LepageInstitut National de la Recherche Agronomique (INRA), Micalis-UMR1319, 78360 Jouy-en-Josas, FranceNadine WaldschmittUniversity of Lille, CNRS, INSERM, Centre Hospitalier Régional Universitaire de Lille, Institut Pasteur de Lille, U1019, UMR 8204, Centre d'Infection et d'Immunité de Lille (CIIL), F-59000 Lille, FranceCaroline FlamentCenter of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, FranceSylvie RusakiewiczCenter of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, FranceBertrand RoutyCenter of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, FranceMaría P. RobertiCenter of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, FranceConnie P.M. DuongCenter of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, FranceVichnou Poirier-ColameCenter of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, FranceAntoine RouxINSERM U1015, GRCC, Villejuif, FranceSonia BecharefCenter of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, FranceSilvia C. FormentiDepartment of Radiation Oncology, New York University, New York, NY, USAEncouse B. GoldenDepartment of Radiation Oncology, New York University, New York, NY, USASascha CordingMicroenvironment and Immunity Unit, Institut Pasteur, Paris, FranceGérard EberlMicroenvironment and Immunity Unit, Institut Pasteur, Paris, FranceAndreas SchlitzerSingapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeFlorent GinhouxSingapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSridhar ManiDepartment of Genetics and Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USATakahiro YamazakiCenter of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, FranceNicolas JacquelotINSERM U1015, GRCC, Villejuif, FranceDavid EnotInstitut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, FranceM BérardAnimalerie Centrale, Institut Pasteur, Paris, FranceJérôme NigouCentre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, FrancePaule OpolonInstitut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, FranceAlexander EggermontDepartment of Medical Oncology, Institut Gustave Roussy, Villejuif, FrancePaul‐Louis WoertherService de microbiologie, GRCC, Villejuif, FranceÉlisabeth ChachatyService de microbiologie, GRCC, Villejuif, FranceNathalie ChaputInstitut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, FranceCaroline RobertDepartment of Medical Oncology, Institut Gustave Roussy, Villejuif, FranceChristina MateusDepartment of Medical Oncology, Institut Gustave Roussy, Villejuif, FranceGuido KroemerEquipe 11 Labellisée—Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, FranceDidier RaoultUnité des Rickettsies, Faculté de Médecine, Université de la Méditerranée, Marseille, FranceIvo G. BonecaINSERM, Equipe Avenir, Paris, FranceFranck CarbonnelGastroenterology Department, Hôpital Bicêtre, Assistance Publique—Hôpitaux de Paris, Paris, FranceMathias ChamaillardUniversity of Lille, CNRS, INSERM, Centre Hospitalier Régional Universitaire de Lille, Institut Pasteur de Lille, U1019, UMR 8204, Centre d'Infection et d'Immunité de Lille (CIIL), F-59000 Lille, FranceLaurence ZitvogelCenter of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, France
2015en
ABI
Аннотация
Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis-specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.
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