Héninger Erika, Krueger Timothy E G, Lang Joshua M
University of Wisconsin Carbone Cancer Center , Madison, WI , USA.
University of Wisconsin Carbone Cancer Center , Madison, WI , USA ; Department of Medicine, University of Wisconsin , Madison, WI , USA.
Front Immunol. 2015 Feb 4;6:29. doi: 10.3389/fimmu.2015.00029. eCollection 2015.
Epigenetic silencing of immune-related genes is a striking feature of the cancer genome that occurs in the process of tumorigenesis. This phenomena impacts antigen processing and antigen presentation by tumor cells and facilitates evasion of immunosurveillance. Further modulation of the tumor microenvironment by altered expression of immunosuppressive cytokines impairs antigen-presenting cells and cytolytic T-cell function. The potential reversal of immunosuppression by epigenetic modulation is therefore a promising and versatile therapeutic approach to reinstate endogenous immune recognition and tumor lysis. Pre-clinical studies have identified multiple elements of the immune system that can be modulated by epigenetic mechanisms and result in improved antigen presentation, effector T-cell function, and breakdown of suppressor mechanisms. Recent clinical studies are utilizing epigenetic therapies prior to, or in combination with, immune therapies to improve clinical outcomes.
免疫相关基因的表观遗传沉默是癌症基因组的一个显著特征，发生在肿瘤发生过程中。这种现象影响肿瘤细胞的抗原加工和抗原呈递，并有助于逃避免疫监视。免疫抑制细胞因子表达改变对肿瘤微环境的进一步调节会损害抗原呈递细胞和细胞毒性T细胞功能。因此，通过表观遗传调节逆转免疫抑制是一种有前景且通用的治疗方法，可恢复内源性免疫识别和肿瘤溶解。临床前研究已经确定了免疫系统的多个元件，这些元件可通过表观遗传机制进行调节，并导致抗原呈递改善、效应T细胞功能增强以及抑制机制的破坏。最近的临床研究正在免疫治疗之前或与之联合使用表观遗传疗法，以改善临床结果。
