Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients.
Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients.
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DOI：
10.1016/j.neo.2017.08.004
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Koh AY
中科院分区：
文献类型：
--
作者：
Frankel AE;Coughlin LA;Kim J;Froehlich TW;Xie Y;Frenkel EP;Koh AY
这是人类肠道微生物区系和代谢产物对转移性黑色素瘤患者免疫检查点抑制物(ICT)反应影响的第一项前瞻性研究。尽管许多黑色素瘤患者对ICT表现出深刻的反应，但ICT失败的患者--特别是患有BRAF野生型疾病的患者--的选择较少。在临床前研究中，特定的肠道微生物区系促进小鼠黑色素瘤的消退。因此，我们对39例转移性黑色素瘤患者用ipilimumab、nivolumab、ipilimumab加nivolumab(IN)或Pembrolizumab(P)治疗前肠道微生物区系和代谢产物对实体瘤ICT反应评估标准的影响进行了研究。有效率67%，病情稳定8%；P组有效率23%，病情稳定23%。所有类型治疗的信息和通信技术应答者都增加了木卡类杆菌。在IN应答者中，肠道微生物群富含普鲁斯尼茨杆菌、类杆菌和丝状霍尔德曼杆菌。在P应答者中，富含Dorea formicenerans的微生物群系。无偏向散弹枪代谢组学显示ICT应答者体内有高水平的羽扇豆酸。在这些初步研究的基础上，有必要对这些细菌种类和代谢物进行额外的验证性临床研究和临床前测试，以确认它们增强ICT的活性。
This is the first prospective study of the effects of human gut microbiota and metabolites on immune checkpoint inhibitor (ICT) response in metastatic melanoma patients. Whereas many melanoma patients exhibit profound response to ICT, there are fewer options for patients failing ICT—particularly with BRAF-wild-type disease. In preclinical studies, specific gut microbiota promotes regression of melanoma in mice. We therefore conducted a study of the effects of pretreatment gut microbiota and metabolites on ICT Response Evaluation Criteria in Solid Tumors response in 39 metastatic melanoma patients treated with ipilimumab, nivolumab, ipilimumab plus nivolumab (IN), or pembrolizumab (P). IN yielded 67% responses and 8% stable disease; P achieved 23% responses and 23% stable disease. ICT responders for all types of therapies were enriched for Bacteroides caccae. Among IN responders, the gut microbiome was enriched for Faecalibacterium prausnitzii, Bacteroides thetaiotamicron, and Holdemania filiformis. Among P responders, the microbiome was enriched for Dorea formicogenerans. Unbiased shotgun metabolomics revealed high levels of anacardic acid in ICT responders. Based on these pilot studies, both additional confirmatory clinical studies and preclinical testing of these bacterial species and metabolites are warranted to confirm their ICT enhancing activity.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
DOI：
10.1056/nejmoa1504030
发表时间：
2015-07-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Larkin J;Chiarion-Sileni V;Gonzalez R;Grob JJ;Cowey CL;Lao CD;Schadendorf D;Dummer R;Smylie M;Rutkowski P;Ferrucci PF;Hill A;Wagstaff J;Carlino MS;Haanen JB;Maio M;Marquez-Rodas I;McArthur GA;Ascierto PA;Long GV;Callahan MK;Postow MA;Grossmann K;Sznol M;Dreno B;Bastholt L;Yang A;Rollin LM;Horak C;Hodi FS;Wolchok JD
通讯作者：
Wolchok JD
影响因子：
5.6
作者：
Gnanaprakasam, J. N. Rashida;Estrada-Muniz, Elizabet;Vega, Libia
通讯作者：
Vega, Libia
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.8
作者：
Hollands, Andrew;Corriden, Ross;Nizet, Victor
通讯作者：
Nizet, Victor