Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota.
Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota.
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DOI：
10.1126/science.aad1329
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发表时间：
2015-11-27
期刊：
影响因子：
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通讯作者：
Zitvogel L
中科院分区：
文献类型：
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作者：
Vétizou M;Pitt JM;Daillère R;Lepage P;Waldschmitt N;Flament C;Rusakiewicz S;Routy B;Roberti MP;Duong CP;Poirier-Colame V;Roux A;Becharef S;Formenti S;Golden E;Cording S;Eberl G;Schlitzer A;Ginhoux F;Mani S;Yamazaki T;Jacquelot N;Enot DP;Bérard M;Nigou J;Opolon P;Eggermont A;Woerther PL;Chachaty E;Chaput N;Robert C;Mateus C;Kroemer G;Raoult D;Boneca IG;Carbonnel F;Chamaillard M;Zitvogel L
靶向CTLA-4的抗体已成功地用作癌症免疫疗法。我们发现CTLA-4阻断的抗肿瘤作用取决于不同的拟杆菌属物种。在小鼠和患者中，特异性针对B.或B。脆弱性与CTLA-4阻断的功效相关。肿瘤治疗或无菌小鼠没有响应CTLA封锁。通过用B管饲克服了该缺陷。fragilis，用B免疫。fragilis多糖，或通过过继转移B。脆性T细胞从人类到小鼠的粪便微生物移植证实，用抗CTLA-4抗体治疗黑色素瘤患者有利于B的生长。fragilis具有抗癌特性。这项研究揭示了类杆菌在CTLA-4阻断的免疫刺激作用中的关键作用。
Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis–specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.