Laboratory for Hematology and Immunology, Department of Biomedical Sciences, Vrije Universiteit Brussel, Brussels, Belgium.
Center for Medical Genetics, Vrije Universiteit Brussel (VUB), Universiteit Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium.
Front Immunol. 2021 Mar 30;12:652160. doi: 10.3389/fimmu.2021.652160. eCollection 2021.
Cancer cells are under the surveillance of the host immune system. Nevertheless, a number of immunosuppressive mechanisms allow tumors to escape protective responses and impose immune tolerance. Epigenetic alterations are central to cancer cell biology and cancer immune evasion. Accordingly, epigenetic modulating agents (EMAs) are being exploited as anti-neoplastic and immunomodulatory agents to restore immunological fitness. By simultaneously acting on cancer cells, e.g. by changing expression of tumor antigens, immune checkpoints, chemokines or innate defense pathways, and on immune cells, e.g. by remodeling the tumor stroma or enhancing effector cell functionality, EMAs can indeed overcome peripheral tolerance to transformed cells. Therefore, combinations of EMAs with chemo- or immunotherapy have become interesting strategies to fight cancer. Here we review several examples of epigenetic changes critical for immune cell functions and tumor-immune evasion and of the use of EMAs in promoting anti-tumor immunity. Finally, we provide our perspective on how EMAs could represent a game changer for combinatorial therapies and the clinical management of cancer.
癌细胞受到宿主免疫系统的监控。然而，许多免疫抑制机制允许肿瘤逃避保护反应并产生免疫耐受。表观遗传改变是癌细胞生物学和癌症免疫逃逸的核心。因此，正在利用表观遗传调节剂 (EMAs) 作为抗肿瘤和免疫调节剂，以恢复免疫适应性。通过同时作用于癌细胞，例如通过改变肿瘤抗原、免疫检查点、趋化因子或先天防御途径的表达，以及作用于免疫细胞，例如通过重塑肿瘤基质或增强效应细胞功能，EMAs 确实可以克服对转化细胞的外周耐受。因此，EMAs 与化疗或免疫疗法的联合已成为对抗癌症的有趣策略。在这里，我们回顾了对免疫细胞功能和肿瘤免疫逃逸至关重要的几种表观遗传变化的例子，以及在促进抗肿瘤免疫方面 EMA 的应用。最后，我们就 EMA 如何成为组合疗法和癌症临床管理的游戏规则改变者提供了我们的看法。
