Fiche publication
Date publication
novembre 2013
Journal
Science (New York, N.Y.)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GHIRINGHELLI François
Tous les auteurs :
Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillère R, Hannani D, Enot DP, Pfirschke C, Engblom C, Pittet MJ, Schlitzer A, Ginhoux F, Apetoh L, Chachaty E, Woerther PL, Eberl G, Bérard M, Ecobichon C, Clermont D, Bizet C, Gaboriau-Routhiau V, Cerf-Bensussan N, Opolon P, Yessaad N, Vivier E, Ryffel B, Elson CO, Doré J, Kroemer G, Lepage P, Boneca IG, Ghiringhelli F, Zitvogel L
Lien Pubmed
Résumé
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.
Mots clés
Adoptive Transfer, Animals, Anti-Bacterial Agents, administration & dosage, Antineoplastic Agents, therapeutic use, Bacterial Translocation, drug effects, Cyclophosphamide, therapeutic use, Germ-Free Life, Gram-Positive Bacteria, drug effects, Immunologic Memory, Immunosuppressive Agents, therapeutic use, Intestine, Small, microbiology, Lymphoid Tissue, immunology, Mice, Microbiota, drug effects, Neoplasms, drug therapy, Th17 Cells, immunology
Référence
Science. 2013 Nov;342(6161):971-6
