Статья

The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide

Sophie ViaudInstitut National de la Santé et de la Recherche Médicale, U1015, Equipe labellisée Ligue Nationale Contre le Cancer, Institut Gustave Roussy, Villejuif, FranceFabiana SaccheriInstitut National de la Santé et de la Recherche Médicale, U1015, Equipe labellisée Ligue Nationale Contre le Cancer, Institut Gustave Roussy, Villejuif, FranceGrégoire MignotInstitut National de la Santé et de la Recherche Médicale, Group Avenir, Dijon, FranceTakahiro YamazakiInstitut National de la Santé et de la Recherche Médicale, U1015, Equipe labellisée Ligue Nationale Contre le Cancer, Institut Gustave Roussy, Villejuif, FranceRomain DaillèreInstitut Gustave RoussyDalil HannaniInstitut National de la Santé et de la Recherche Médicale, U1015, Equipe labellisée Ligue Nationale Contre le Cancer, Institut Gustave Roussy, Villejuif, FranceDavid EnotInstitut National de la Santé et de la Recherche Médicale, U848, Institut Gustave Roussy, Villejuif, FranceChristina PfirschkeCenter for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USACamilla EngblomCenter for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USAMikaël J. PittetCenter for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USAAndreas SchlitzerSingapore Immunology Network (SIgN), Agency for Science, Technology and Research (A* STAR), SingaporeFlorent GinhouxSingapore Immunology Network (SIgN), Agency for Science, Technology and Research (A* STAR), SingaporeLionel ApétohInstitut National de la Santé et de la Recherche Médicale, Group Avenir, Dijon, FranceÉlisabeth ChachatyService de Microbiologie, Institut Gustave Roussy, Villejuif, FrancePaul‐Louis WoertherService de Microbiologie, Institut Gustave Roussy, Villejuif, FranceGérard EberlLymphoid Tissue Development Unit, Institut Pasteur, Paris, FranceM BérardNimalerie Centrale, Institut Pasteur, Paris, FranceChantal EcobichonInstitut National de la Santé et de la Recherche Médicale, Group Avenir, Paris, FranceDominique ClermontInstitut Pasteur, Collection de l’Institut Pasteur, Paris, FranceChantal BizetInstitut Pasteur, Collection de l’Institut Pasteur, Paris, FranceValérie Gaboriau‐RouthiauInstitut National de la Recherche Agronomique, Micalis–UMR1319, 78350 Jouy-en-Josas, FranceNadine Cerf–BensussanInstitut National de la Recherche Agronomique, Micalis–UMR1319, 78350 Jouy-en-Josas, FrancePaule OpolonInstitut Gustave Roussy, IFR54, Villejuif, FranceNadia YessaadAssistance Publique des Hôpitaux de Marseille, Hôpital de la Conception, Marseille, FranceÉric VivierAssistance Publique des Hôpitaux de Marseille, Hôpital de la Conception, Marseille, FranceBernhard RyffelLaboratory of Molecular and Experimental Immunology and Neurogenetics, UMR 7355, CNRS-University of Orleans, Orleans, FranceCharles O. ElsonUniversity of Alabama at Birmingham, Birmingham, AL, USAJoël DoréAgroParisTech, Micalis–UMR1319, 78352 Jouy-en-Josas, FranceGuido KroemerEquipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, FrancePatricia LepageAgroParisTech, Micalis–UMR1319, 78352 Jouy-en-Josas, FranceIvo G. BonecaInstitut National de la Santé et de la Recherche Médicale, Group Avenir, Paris, FranceFrançois GhiringhelliFaculté de Médecine, Université de Bourgogne, Dijon, FranceLaurence ZitvogelCentre d’Investigation Clinique Biothérapie CICBT 507, Institut Gustave Roussy, Villejuif, France

2013en

ABI

Аннотация

Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate antitumor immune responses. Studying mouse models, we demonstrate that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram-positive bacteria into secondary lymphoid organs. There, these bacteria stimulate the generation of a specific subset of "pathogenic" T helper 17 (pT(H)17) cells and memory T(H)1 immune responses. Tumor-bearing mice that were germ-free or that had been treated with antibiotics to kill Gram-positive bacteria showed a reduction in pT(H)17 responses, and their tumors were resistant to cyclophosphamide. Adoptive transfer of pT(H)17 cells partially restored the antitumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response.

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Идентификаторы

DOI: 10.1126/science.1240537

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar