美国洛克菲勒大学Howard C. Hang研究小组发现，肠球菌肽聚糖的重塑促进检查点抑制剂的癌症免疫治疗。这一研究成果于2021年8月27日发表在国际学术期刊《科学》上。

研究人员表明肠球菌属的成员能改善小鼠肿瘤模型中检查点抑制剂的免疫疗法。活跃的肠球菌表达和分泌NlpC/p60肽聚糖水解酶SagA的同源物，产生免疫活性的膜肽。SagA在非保护性粪肠球菌中的表达足以促进免疫治疗反应，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的神经肽也增强了抗PD-L1的抗肿瘤疗效。这些数据表明，具有专门肽聚糖重塑活性的微生物群物种和基于胞壁肽的治疗方法可以增强癌症免疫治疗，并可作为下一代佐剂加以利用。

据介绍，癌症免疫疗法的抗肿瘤疗效可能与肠道微生物组中某些细菌物种的存在相关。然而，影响宿主对免疫疗法反应的许多分子机制仍然难以捉摸。

附：英文原文

Title: Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy

Author: Matthew E. Griffin, Juliel Espinosa, Jessica L. Becker, Ji-Dung Luo, Thomas S. Carroll, Jyoti K. Jha, Gary R. Fanger, Howard C. Hang

Issue&Volume: 2021/08/27

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.

DOI: 10.1126/science.abc9113

Source: https://science.sciencemag.org/content/373/6558/1040