Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients

doi:10.1126/science.abf3363

GSTDTAP > 气候变化

DOI	10.1126/science.abf3363
	Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients
	Diwakar Davar; Amiran K. Dzutsev; John A. McCulloch; Richard R. Rodrigues; Joe-Marc Chauvin; Robert M. Morrison; Richelle N. Deblasio; Carmine Menna; Quanquan Ding; Ornella Pagliano; Bochra Zidi; Shuowen Zhang; Jonathan H. Badger; Marie Vetizou; Alicia M. Cole; Miriam R. Fernandes; Stephanie Prescott; Raquel G. F. Costa; Ascharya K. Balaji; Andrey Morgun; Ivan Vujkovic-Cvijin; Hong Wang; Amir A. Borhani; Marc B. Schwartz; Howard M. Dubner; Scarlett J. Ernst; Amy Rose; Yana G. Najjar; Yasmine Belkaid; John M. Kirkwood; Giorgio Trinchieri; Hassane M. Zarour
	2021-02-05
发表期刊	Science
出版年	2021
英文摘要	The composition of the gut microbiome influences the response of cancer patients to immunotherapies. Baruch et al. and Davar et al. report first-in-human clinical trials to test whether fecal microbiota transplantation (FMT) can affect how metastatic melanoma patients respond to anti–PD-1 immunotherapy (see the Perspective by Woelk and Snyder). Both studies observed evidence of clinical benefit in a subset of treated patients. This included increased abundance of taxa previously shown to be associated with response to anti–PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8–expressing myeloid cells, which are involved in immunosuppression. These studies provide proof-of-concept evidence for the ability of FMT to affect immunotherapy response in cancer patients. Science , this issue p. [602][1], p. [595][2]; see also p. [573][3] Anti–programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti–PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti–PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti–PD-1 in patients with PD-1–refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti–PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8–expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti–PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti–PD-1 in a subset of PD-1 advanced melanoma. [1]: /lookup/doi/10.1126/science.abb5920 [2]: /lookup/doi/10.1126/science.abf3363 [3]: /lookup/doi/10.1126/science.abg2904
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/314047
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Diwakar Davar,Amiran K. Dzutsev,John A. McCulloch,等. Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients[J]. Science,2021.
APA	Diwakar Davar.,Amiran K. Dzutsev.,John A. McCulloch.,Richard R. Rodrigues.,Joe-Marc Chauvin.,...&Hassane M. Zarour.(2021).Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients.Science.
MLA	Diwakar Davar,et al."Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients".Science (2021).