Viaud S, Daillère R, Boneca I G, Lepage P, Langella P, Chamaillard M, Pittet M J, Ghiringhelli F, Trinchieri G, Goldszmid R, Zitvogel L
1] Institut National de la Santé et de la Recherche Médicale, U1015 INSERM, Gustave Roussy, Villejuif, France [2] Université Paris-Sud, Kremlin Bicêtre, France.
1] Institut Pasteur, Unit Biology and Genetics of the Bacterial Cell Wall, Paris, France [2] Institut National de la Santé et de la Recherche Médicale, Group Avenir, Paris, France.
Cell Death Differ. 2015 Feb;22(2):199-214. doi: 10.1038/cdd.2014.56. Epub 2014 May 16.
The impact of gut microbiota in eliciting innate and adaptive immune responses beneficial for the host in the context of effective therapies against cancer has been highlighted recently. Chemotherapeutic agents, by compromising, to some extent, the intestinal integrity, increase the gut permeability and selective translocation of Gram-positive bacteria in secondary lymphoid organs. There, anticommensal pathogenic Th17 T-cell responses are primed, facilitating the accumulation of Th1 helper T cells in tumor beds after chemotherapy as well as tumor regression. Importantly, the redox equilibrium of myeloid cells contained in the tumor microenvironment is also influenced by the intestinal microbiota. Hence, the anticancer efficacy of alkylating agents (such as cyclophosphamide) and platinum salts (oxaliplatin, cis-platin) is compromised in germ-free mice or animals treated with antibiotics. These findings represent a paradigm shift in our understanding of the mode of action of many compounds having an impact on the host-microbe mutualism.
最近,肠道微生物群在引发对宿主有益的先天性和适应性免疫反应方面的影响在针对癌症的有效治疗背景下得到了突出强调。化疗药物在一定程度上破坏肠道完整性,增加肠道通透性以及革兰氏阳性菌在次级淋巴器官中的选择性易位。在那里,引发抗共生致病性Th17 T细胞反应,促进化疗后肿瘤床中Th1辅助性T细胞的积累以及肿瘤消退。重要的是,肿瘤微环境中髓样细胞的氧化还原平衡也受肠道微生物群影响。因此,在无菌小鼠或用抗生素治疗的动物中,烷化剂(如环磷酰胺)和铂盐(奥沙利铂、顺铂)的抗癌功效会受到损害。这些发现代表了我们对许多影响宿主 - 微生物共生关系的化合物作用方式理解上的范式转变。