title: Harnessing the intestinal microbiome for optimal therapeutic immunomodulation.
abstract: Distinct cytotoxic agents currently used in the oncological armamentarium mediate their clinical benefit by influencing, directly or indirectly, the immune system in such a way that innate and adaptive immunity contributes to the tumoricidal activity. Now, we bring up evidence that both arms of anticancer immunity can be triggered through the intervention of the intestinal microbiota. Alkylating agents, such as cyclophosphamide, set up the stage for enhanced permeability of the small intestine, facilitating the translocation of selected arrays of Gram-positive bacteria against which the host mounts effector pTh17 cells and memory Th1 responses. In addition, gut commensals, through lipopolysaccharide and other bacterial components, switch the tumor microenvironment, in particular the redox equilibrium and the TNF production of intratumoral myeloid cells during therapies with platinum salts or intratumoral TLR9 agonists combined with systemic anti-IL10R Ab respectively. Consequently, antibiotics can compromise the efficacy of certain chemotherapeutic or immunomodulatory regimens.
authors: Institut National de la Santé et de la Recherche Médicale, U1015, Gustave Roussy, Villejuif, France. Université Paris-Sud, Kremlin Bicêtre, France.
authors: S
authors: S
authors: Viaud
authors: Institut National de la Santé et de la Recherche Médicale, U1015, Gustave Roussy, Villejuif, France. Université Paris-Sud, Kremlin Bicêtre, France.
authors: R
authors: R
authors: Daillère
authors: Institut Pasteur, Unit Biology and Genetics of the Bacterial Cell Wall, Paris, France. Institut National de la Santé et de la Recherche Médicale, Group Avenir, Paris, France.
authors: I G
authors: IG
authors: Boneca
authors: Institut National de la Recherche Agronomique, Micalis UMR1319, Jouy-en-Josas, France. AgroParisTech, Micalis UMR1319, Jouy-en-Josas, France.
authors: P
authors: P
authors: Lepage
authors: Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors: M J
authors: MJ
authors: Pittet
authors: Institut National de la Santé et de la Recherche Médicale, U866, Centre Georges François Leclerc, Dijon, France. Institut National de la Santé et de la Recherche Médicale, Group Avenir, Dijon, France. Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors: F
authors: F
authors: Ghiringhelli
authors: Cancer and Inflammation Program, National Cancer Institute, Frederick, Maryland.
authors: G
authors: G
authors: Trinchieri
authors: Cancer and Inflammation Program, National Cancer Institute, Frederick, Maryland.
authors: R
authors: R
authors: Goldszmid
authors: Institut National de la Santé et de la Recherche Médicale, U1015, Gustave Roussy, Villejuif, France. Université Paris-Sud, Kremlin Bicêtre, France. Centre d'Investigation Clinique Biothérapie CICBT 507, Gustave Roussy, Villejuif, France. laurence.zitvogel@gustaveroussy.fr.
authors: L
authors: L
authors: Zitvogel
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation / Q000276:immunology; D007422:Intestines / Q000276:immunology* / Q000382:microbiology*; D064307:Microbiota / Q000276:immunology*; D015398:Signal Transduction