EZH2，实体瘤微环境和免疫治疗的遗传与表观遗传调控的重要协调因子。

EZH2, a prominent orchestrator of genetic and epigenetic regulation of solid tumor microenvironment and immunotherapy.

作者信息

Sun Shanshan, Yu Feng, Xu Danying, Zheng Haiyan, Li Min

机构信息

Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Cancer Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Department of Medicine, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America; Department of Surgery, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.

Cancer Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

出版信息

Biochim Biophys Acta Rev Cancer. 2022 Mar;1877(2):188700. doi: 10.1016/j.bbcan.2022.188700. Epub 2022 Feb 22.

DOI:10.1016/j.bbcan.2022.188700

PMID:35217116

Abstract

Immune checkpoint blockade (ICB) is regarded as a promising strategy for cancer therapy. The histone methyltransferase, Enhancer of Zeste Homolog 2 (EZH2), has been implicated in the carcinogenesis of numerous solid tumors. However, the underlying mechanism of EZH2 in cancer immunotherapeutic resistance remains unknown. EZH2 orchestrates the regulation of the innate and adaptive immune systems of the tumor microenvironment (TME). Profound epigenetic and transcriptomic changes induced by EZH2 in tumor cells and immune cells mobilize the elements of the TME, leading to immune-suppressive activity of solid tumors. In this review, we summarized the dynamic functions of EZH2 on the different components of the TME, including tumor cells, T cells, macrophages, natural killer cells, myeloid-derived suppressor cells, dendritic cells, fibroblasts, and mesenchymal stem cells. Several ongoing anti-tumor clinical trials using EZH2 inhibitors have also been included as translational perspectives. In conclusion, based combinational therapy to enable ICB could offer a survival benefit in patients with cancer.

摘要

免疫检查点阻断（ICB）被认为是一种很有前景的癌症治疗策略。组蛋白甲基转移酶Zeste同源物2增强子（EZH2）与多种实体瘤的致癌作用有关。然而，EZH2在癌症免疫治疗耐药中的潜在机制仍不清楚。EZH2协调肿瘤微环境（TME）的固有和适应性免疫系统的调节。EZH2在肿瘤细胞和免疫细胞中诱导的深刻表观遗传和转录组变化调动了TME的要素，导致实体瘤的免疫抑制活性。在这篇综述中，我们总结了EZH2对TME不同组成部分的动态作用，包括肿瘤细胞、T细胞、巨噬细胞、自然杀伤细胞、髓源性抑制细胞、树突状细胞、成纤维细胞和间充质干细胞。一些正在进行的使用EZH2抑制剂的抗肿瘤临床试验也作为转化前景被纳入。总之，基于联合治疗以实现ICB可能会给癌症患者带来生存益处。