Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.
Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.
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DOI：
10.1126/science.aan4236
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发表时间：
2018-01-05
期刊：
影响因子：
--
通讯作者：
Wargo JA
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文献类型：
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作者：
Gopalakrishnan V;Spencer CN;Nezi L;Reuben A;Andrews MC;Karpinets TV;Prieto PA;Vicente D;Hoffman K;Wei SC;Cogdill AP;Zhao L;Hudgens CW;Hutchinson DS;Manzo T;Petaccia de Macedo M;Cotechini T;Kumar T;Chen WS;Reddy SM;Szczepaniak Sloane R;Galloway-Pena J;Jiang H;Chen PL;Shpall EJ;Rezvani K;Alousi AM;Chemaly RF;Shelburne S;Vence LM;Okhuysen PC;Jensen VB;Swennes AG;McAllister F;Marcelo Riquelme Sanchez E;Zhang Y;Le Chatelier E;Zitvogel L;Pons N;Austin-Breneman JL;Haydu LE;Burton EM;Gardner JM;Sirmans E;Hu J;Lazar AJ;Tsujikawa T;Diab A;Tawbi H;Glitza IC;Hwu WJ;Patel SP;Woodman SE;Amaria RN;Davies MA;Gershenwald JE;Hwu P;Lee JE;Zhang J;Coussens LM;Cooper ZA;Futreal PA;Daniel CR;Ajami NJ;Petrosino JF;Tetzlaff MT;Sharma P;Allison JP;Jenq RR;Wargo JA
临床前小鼠模型表明，肠道微生物组调节肿瘤对检查点阻断免疫疗法的反应;然而，这在人类癌症患者中尚未得到充分表征。在这里，我们检查了接受抗程序性细胞死亡1蛋白（PD-1）免疫治疗的黑色素瘤患者（n= 112）的口腔和肠道微生物组。观察到应答者与非应答者的患者肠道微生物组的多样性和组成存在显著差异。患者粪便微生物组样品的分析（n= 43，30个应答者，13个无应答者）显示应答患者中显著更高的α多样性（P< 0.01）和瘤胃球菌科细菌的相对丰度（P< 0.01）。宏基因组研究揭示了应答者肠道细菌的功能差异，包括合成代谢途径的富集。免疫分析表明，具有良好肠道微生物组的应答患者以及接受应答患者粪便移植的无菌小鼠的全身和抗肿瘤免疫力增强。总之，这些数据对使用免疫检查点抑制剂治疗黑色素瘤患者具有重要意义。
Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti–programmed cell death 1 protein (PD-1) immunotherapy (n= 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n= 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P< 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P< 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.
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影响因子：
45.3
作者：
Peled, Jonathan U.;Devlin, Sean M.;van den Brink, Marcel R. M.
通讯作者：
van den Brink, Marcel R. M.
影响因子：
10.1
作者：
Johnson DB;Frampton GM;Rioth MJ;Yusko E;Xu Y;Guo X;Ennis RC;Fabrizio D;Chalmers ZR;Greenbowe J;Ali SM;Balasubramanian S;Sun JX;He Y;Frederick DT;Puzanov I;Balko JM;Cates JM;Ross JS;Sanders C;Robins H;Shyr Y;Miller VA;Stephens PJ;Sullivan RJ;Sosman JA;Lovly CM
通讯作者：
Lovly CM
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
28.2
作者：
Chen PL;Roh W;Reuben A;Cooper ZA;Spencer CN;Prieto PA;Miller JP;Bassett RL;Gopalakrishnan V;Wani K;De Macedo MP;Austin-Breneman JL;Jiang H;Chang Q;Reddy SM;Chen WS;Tetzlaff MT;Broaddus RJ;Davies MA;Gershenwald JE;Haydu L;Lazar AJ;Patel SP;Hwu P;Hwu WJ;Diab A;Glitza IC;Woodman SE;Vence LM;Wistuba II;Amaria RN;Kwong LN;Prieto V;Davis RE;Ma W;Overwijk WW;Sharpe AH;Hu J;Futreal PA;Blando J;Sharma P;Allison JP;Chin L;Wargo JA
通讯作者：
Wargo JA
DOI：
10.1126/science.1198719
发表时间：
2011-05-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Muegge BD;Kuczynski J;Knights D;Clemente JC;González A;Fontana L;Henrissat B;Knight R;Gordon JI
通讯作者：
Gordon JI