Role of the intestinal microbiome and microbial-derived metabolites in immune checkpoint blockade immunotherapy of cancer.
Role of the intestinal microbiome and microbial-derived metabolites in immune checkpoint blockade immunotherapy of cancer.
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肠道微生物组和微生物衍生代谢物在癌症免疫检查点阻断免疫治疗中的作用。
DOI：
10.1186/s13073-021-00923-w
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发表时间：
2021-06-23
期刊：
影响因子：
12.3
通讯作者：
Jenq RR
中科院分区：
文献类型：
--
作者：
Hayase E;Jenq RR
免疫检查点抑制剂（ICI）是阻断免疫抑制途径的单克隆抗体。ICIs的施用增强了T细胞介导的针对肿瘤的免疫应答，从而改善了癌症患者的总体存活率。已经出现的是，肠道微生物组可以通过宿主免疫系统调节对ICI的反应，并且抗生素的使用可以导致ICI的功效降低。最近，有报道称，粪便微生物群移植可导致先前治疗难治性患者的ICI治疗反应，这表明靶向微生物群可能是重新编程肿瘤微环境和增强ICI治疗的可行策略。肠道微生物代谢产物也可能与ICI的应答率有关。除了反应率之外，还发现ICI治疗期间可能出现的某些毒性与肠道微生物组相关，特别是结肠炎。一个关键的机制问题是某些微生物如何增强抗肿瘤反应，或者易患ICI相关结肠炎。有证据表明，肠道微生物组可以通过两种主要机制调节ICI治疗的结果，包括抗原特异性机制和抗原非依赖性机制。抗原特异性机制发生在微生物和肿瘤抗原之间共享表位时，其可以通过交叉反应性适应性免疫细胞增强或减少抗肿瘤免疫应答。抗原非依赖性机制包括通过接合先天和/或适应性免疫细胞来调节对ICI的反应。为了建立基于微生物组的结果生物标志物并特异性调节肠道微生物组以增强ICI在癌症免疫治疗中的疗效，需要进一步的前瞻性干预研究。
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block immune inhibitory pathways. Administration of ICIs augments T cell-mediated immune responses against tumor, resulting in improved overall survival in cancer patients. It has emerged that the intestinal microbiome can modulate responses to ICIs via the host immune system and that the use of antibiotics can lead to reduced efficacy of ICIs. Recently, reports that fecal microbiota transplantation can lead to ICI therapy responses in patients previously refractory to therapy suggest that targeting the microbiome may be a viable strategy to reprogram the tumor microenvironment and augment ICI therapy. Intestinal microbial metabolites may also be linked to response rates to ICIs. In addition to response rates, certain toxicities that can arise during ICI therapy have also been found to be associated with the intestinal microbiome, including in particular colitis. A key mechanistic question is how certain microbes can enhance anti-tumor responses or, alternatively, predispose to ICI-associated colitis. Evidence has emerged that the intestinal microbiome can modulate outcomes to ICI therapies via two major mechanisms, including those that are antigen-specific and those that are antigen-independent. Antigen-specific mechanisms occur when epitopes are shared between microbial and tumor antigens that could enhance, or, alternatively, reduce anti-tumor immune responses via cross-reactive adaptive immune cells. Antigen-independent mechanisms include modulation of responses to ICIs by engaging innate and/or adaptive immune cells. To establish microbiome-based biomarkers of outcomes and specifically modulate the intestinal microbiome to enhance efficacy of ICIs in cancer immunotherapy, further prospective interventional studies will be required.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
82.9
作者：
Gros A;Parkhurst MR;Tran E;Pasetto A;Robbins PF;Ilyas S;Prickett TD;Gartner JJ;Crystal JS;Roberts IM;Trebska-McGowan K;Wunderlich JR;Yang JC;Rosenberg SA
通讯作者：
Rosenberg SA
影响因子：
64.8
作者：
Helmink BA;Reddy SM;Gao J;Zhang S;Basar R;Thakur R;Yizhak K;Sade-Feldman M;Blando J;Han G;Gopalakrishnan V;Xi Y;Zhao H;Amaria RN;Tawbi HA;Cogdill AP;Liu W;LeBleu VS;Kugeratski FG;Patel S;Davies MA;Hwu P;Lee JE;Gershenwald JE;Lucci A;Arora R;Woodman S;Keung EZ;Gaudreau PO;Reuben A;Spencer CN;Burton EM;Haydu LE;Lazar AJ;Zapassodi R;Hudgens CW;Ledesma DA;Ong S;Bailey M;Warren S;Rao D;Krijgsman O;Rozeman EA;Peeper D;Blank CU;Schumacher TN;Butterfield LH;Zelazowska MA;McBride KM;Kalluri R;Allison J;Petitprez F;Fridman WH;Sautès-Fridman C;Hacohen N;Rezvani K;Sharma P;Tetzlaff MT;Wang L;Wargo JA
通讯作者：
Wargo JA
影响因子：
7.4
作者：
Botticelli, Andrea;Vernocchi, Pamela;Marchetti, Paolo
通讯作者：
Marchetti, Paolo
影响因子：
16.6
作者：
Dubin K;Callahan MK;Ren B;Khanin R;Viale A;Ling L;No D;Gobourne A;Littmann E;Huttenhower C;Pamer EG;Wolchok JD
通讯作者：
Wolchok JD