文章：

肠球菌肽聚糖重塑促进检查点抑制剂癌症免疫治疗

Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy

原文发布日期：2021-08-26

DOI: 10.1126/science.abc9113

类型: Report

开放获取: 否

文章简介：

SagA promotes immunotherapy response

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. —PNK

Abstract

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.

简介翻译： 

SagA 促进免疫治疗反应

肠道微生物组可以影响接受PD-L1免疫治疗的癌症患者的治疗结果，但有利反应的机制尚不清楚。Griffin等人发现一种称为肠球菌的特定类型细菌在小鼠中增强抗PD-L1免疫治疗（参见Ansaldo和Belkaid的视角）。研究人员显示，肠球菌分泌一种称为SagA的酶，该酶分解细菌细胞壁的组成部分。这个过程导致胞壁肽片段的释放，这些片段随后作为刺激分子促进先天免疫传感器蛋白NOD2的信号传导，并改善免疫治疗反应。—PNK

摘要

癌症免疫治疗的抗肿瘤功效可能与肠道微生物组中某些细菌物种的存在相关。然而，影响宿主对免疫治疗反应的许多分子机制仍然难以捉摸。在这项研究中，我们显示肠球菌属的成员在小鼠肿瘤模型中改善检查点抑制剂免疫治疗。活性肠球菌表达并分泌NlpC/p60肽聚糖水解酶SagA的同源物，这些同源物产生免疫活性的胞壁肽。在非保护性粪肠球菌中表达SagA足以促进免疫治疗反应，并且其活性需要肽聚糖传感器NOD2。值得注意的是，SagA工程化的益生菌或合成胞壁肽也增强了抗PD-L1抗肿瘤功效。总之，我们的数据表明，具有专门肽聚糖重塑活性的微生物物种和基于胞壁肽的治疗方法可能增强癌症免疫治疗，并可能被用作下一代佐剂。

原文链接：

Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy