肿瘤细胞治疗研究
英文原题：EZH2, a prominent orchestrator of genetic and epigenetic regulation of solid tumor microenvironment and immunotherapy.
基于联合治疗以启用ICB可能为癌症患者提供生存获益。
免疫检查点阻断（ICB）被认为是癌症治疗的一种有前景的策略。组蛋白甲基转移酶zeste同源物增强子2（EZH2）已被认为与多种实体瘤的癌变有关。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）中固有免疫系统和适应性免疫系统的调控。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动员了TME的各个要素，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不同组分的动态功能，包括肿瘤细胞、T细胞、巨噬细胞、NK 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。几项正在进行的使用EZH2抑制剂的抗肿瘤临床试验也被纳入作为转化前景。总之，基于联合治疗以使ICB成为可能，可能为癌症患者提供生存获益。
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.
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