Harnessing the intestinal microbiome for optimal therapeutic immunomodulation

S. Viaud, R. Daillère, I. G. Boneca, P. Lepage, M. J. Pittet, F. Ghiringhelli, G. Trinchieri, R. Goldszmid, Laurence Zitvoge

    Résultats de recherche: Contribution à un journalArticle 'review'Revue par des pairs

    39 Citations (Scopus)

    Résumé

    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.

    langue originaleAnglais
    Pages (de - à)4217-4221
    Nombre de pages5
    journalCancer Research
    Volume74
    Numéro de publication16
    Les DOIs
    étatPublié - 15 août 2014

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