Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy

doi:10.1126/science.abc3421

GSTDTAP > 气候变化

DOI	10.1126/science.abc3421
	Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy
	Lukas F. Mager; Regula Burkhard; Nicola Pett; Noah C. A. Cooke; Kirsty Brown; Hena Ramay; Seungil Paik; John Stagg; Ryan A. Groves; Marco Gallo; Ian A. Lewis; Markus B. Geuking; Kathy D. McCoy
	2020-09-18
发表期刊	Science
出版年	2020
英文摘要	Checkpoint blockade immunotherapy harnesses the immune system to kill cancer cells and has been used with great success to treat certain tumors, but not all cancer patients respond. The efficacy of checkpoint blockade immunotherapy has been shown to depend on the presence of distinct, beneficial bacteria residing in the gut of patients, but how the microbiome mediates such beneficial effects is unclear. Mager et al. found that specific bacteria produce a metabolite called inosine that enhances the effect of checkpoint blockade immunotherapy (see the Perspective by Shaikh and Sears). In mouse models, inosine, together with proinflammatory stimuli and immunotherapy, strongly enhanced the antitumor capacities of T cells in multiple tumor types, including colorectal cancer, bladder cancer, and melanoma. Science , this issue p. [1481][1]; see also p. [1427][2] Several species of intestinal bacteria have been associated with enhanced efficacy of checkpoint blockade immunotherapy, but the underlying mechanisms by which the microbiome enhances antitumor immunity are unclear. In this study, we isolated three bacterial species— Bifidobacterium pseudolongum , Lactobacillus johnsonii , and Olsenella species—that significantly enhanced efficacy of immune checkpoint inhibitors in four mouse models of cancer. We found that intestinal B. pseudolongum modulated enhanced immunotherapy response through production of the metabolite inosine. Decreased gut barrier function induced by immunotherapy increased systemic translocation of inosine and activated antitumor T cells. The effect of inosine was dependent on T cell expression of the adenosine A2A receptor and required costimulation. Collectively, our study identifies a previously unknown microbial metabolite immune pathway activated by immunotherapy that may be exploited to develop microbial-based adjuvant therapies. [1]: /lookup/doi/10.1126/science.abc3421 [2]: /lookup/doi/10.1126/science.abe0709
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/295427
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Lukas F. Mager,Regula Burkhard,Nicola Pett,et al. Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy[J]. Science,2020.
APA	Lukas F. Mager.,Regula Burkhard.,Nicola Pett.,Noah C. A. Cooke.,Kirsty Brown.,...&Kathy D. McCoy.(2020).Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy.Science.
MLA	Lukas F. Mager,et al."Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy".Science (2020).