<em>Enterococcus</em> peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy

doi:10.1126/science.abc9113

GSTDTAP > 气候变化

DOI	10.1126/science.abc9113
	Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy
	Matthew E. Griffin; Juliel Espinosa; Jessica L. Becker; Ji-Dung Luo; Thomas S. Carroll; Jyoti K. Jha; Gary R. Fanger; Howard C. Hang
	2021-08-27
发表期刊	Science
出版年	2021
英文摘要	The gut microbiome can influence the treatment outcome for cancer patients receiving PD-L1 immunotherapy, but the mechanisms underlying favorable responses are unclear. Griffin et al. found that a particular type of bacteria called enterococci enhance anti–PD-L1 immunotherapy in mice (see the Perspective by Ansaldo and Belkaid). The researchers show that enterococci secrete an enzyme called SagA that breaks down components of the bacterial cell wall. This process results in the release of muramyl peptide fragments, which in turn act as stimulatory molecules to promote signaling of the innate immune sensor protein NOD2 and improved immunotherapy responses. Science , abc9113, this issue p. [1040][1]; see also abl3656, p. [966][2] The antitumor efficacy of cancer immunotherapy can correlate with the presence of certain bacterial species within the gut microbiome. However, many of the molecular mechanisms that influence host response to immunotherapy remain elusive. In this study, we show that members of the bacterial genus Enterococcus improve checkpoint inhibitor immunotherapy in mouse tumor models. Active enterococci express and secrete orthologs of the NlpC/p60 peptidoglycan hydrolase SagA that generate immune-active muropeptides. Expression of SagA in nonprotective E. faecalis was sufficient to promote immunotherapy response, and its activity required the peptidoglycan sensor NOD2. Notably, SagA-engineered probiotics or synthetic muropeptides also augmented anti–PD-L1 antitumor efficacy. Taken together, our data suggest that microbiota species with specialized peptidoglycan remodeling activity and muropeptide-based therapeutics may enhance cancer immunotherapy and could be leveraged as next-generation adjuvants. [1]: /lookup/doi/10.1126/science.abc9113 [2]: /lookup/doi/10.1126/science.abl3656
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/336675
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Matthew E. Griffin,Juliel Espinosa,Jessica L. Becker,et al. Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy[J]. Science,2021.
APA	Matthew E. Griffin.,Juliel Espinosa.,Jessica L. Becker.,Ji-Dung Luo.,Thomas S. Carroll.,...&Howard C. Hang.(2021).Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy.Science.
MLA	Matthew E. Griffin,et al."Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy".Science (2021).