Department of Experimental Therapeutics, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC, V5Z 1L3, Canada.
Belgian Volition SPRL, Parc Scientifique Créalys, Rue Phocas Lejeune 22, BE-5032 Isnes, Belgium.
Epigenomics. 2020 Aug;12(16):1457-1476. doi: 10.2217/epi-2020-0186. Epub 2020 Sep 17.
Immunotherapies are revolutionizing the clinical management of a wide range of cancers. However, intrinsic or acquired unresponsiveness to immunotherapies does occur due to the dynamic cancer immunoediting which ultimately leads to immune escape. The evolutionarily conserved histone modifier enhancer of zeste 2 (EZH2) is aberrantly overexpressed in a number of human cancers. Accumulating studies indicate that EZH2 is a main driver of cancer cells' immunoediting and mediate immune escape through downregulating immune recognition and activation, upregulating immune checkpoints and creating an immunosuppressive tumor microenvironment. In this review, we overviewed the roles of EZH2 in cancer immunoediting, the preclinical and clinical studies of current pharmacologic EZH2 inhibitors and the prospects for EZH2 inhibitor and immunotherapy combination for cancer treatment.
免疫疗法正在彻底改变多种癌症的临床治疗。然而,由于癌症免疫编辑的动态变化,最终导致免疫逃逸,内在或获得性的免疫疗法无应答确实会发生。组蛋白修饰增强子结合锌指蛋白 2(EZH2)在许多人类癌症中异常过表达。越来越多的研究表明,EZH2 是癌细胞免疫编辑的主要驱动因素,并通过下调免疫识别和激活、上调免疫检查点和创建免疫抑制肿瘤微环境来介导免疫逃逸。在这篇综述中,我们概述了 EZH2 在癌症免疫编辑中的作用、目前药理 EZH2 抑制剂的临床前和临床研究,以及 EZH2 抑制剂与免疫疗法联合治疗癌症的前景。