Molecular Oncology Unit, Centro de Investigaciones Energéticas, Medioambientales Y Tecnológicas (CIEMAT), 28040, Madrid, Spain.
Biomedical Research Institute I+12, University Hospital "12 de Octubre", 28041, Madrid, Spain.
Clin Epigenetics. 2021 Mar 24;13(1):63. doi: 10.1186/s13148-021-01046-0.
Epigenetic alterations are known contributors to cancer development and aggressiveness. Additional to alterations in cancer cells, aberrant epigenetic marks are present in cells of the tumor microenvironment, including lymphocytes and tumor-associated macrophages, which are often overlooked but known to be a contributing factor to a favorable environment for tumor growth. Therefore, the main aim of this review is to give an overview of the epigenetic alterations affecting immune cells in the tumor microenvironment to provoke an immunosuppressive function and contribute to cancer development. Moreover, immunotherapy is briefly discussed in the context of epigenetics, describing both its combination with epigenetic drugs and the need for epigenetic biomarkers to predict response to immune checkpoint blockage.
Combining both topics, epigenetic machinery plays a central role in generating an immunosuppressive environment for cancer growth, which creates a barrier for immunotherapy to be successful. Furthermore, epigenetic-directed compounds may not only affect cancer cells but also immune cells in the tumor microenvironment, which could be beneficial for the clinical response to immunotherapy.
Thus, modulating epigenetics in combination with immunotherapy might be a promising therapeutic option to improve the success of this therapy. Further studies are necessary to (1) understand in depth the impact of the epigenetic machinery in the tumor microenvironment; (2) how the epigenetic machinery can be modulated according to tumor type to increase response to immunotherapy and (3) find reliable biomarkers for a better selection of patients eligible to immunotherapy.
表观遗传改变是癌症发生和侵袭性的已知促成因素。除了癌细胞中的改变外，肿瘤微环境中的细胞也存在异常的表观遗传标记，包括淋巴细胞和肿瘤相关巨噬细胞，这些细胞经常被忽视，但已知是促进肿瘤生长的有利环境的促成因素。因此，本综述的主要目的是概述影响肿瘤微环境中免疫细胞的表观遗传改变，以引发免疫抑制功能并促进癌症发展。此外，本文还简要讨论了表观遗传学中的免疫疗法，描述了其与表观遗传药物的联合应用以及需要表观遗传生物标志物来预测对免疫检查点阻断的反应。
将这两个主题结合起来，表观遗传机制在为癌症生长产生免疫抑制环境方面发挥着核心作用，这为免疫疗法的成功设置了障碍。此外，表观遗传靶向化合物不仅可以影响癌细胞，还可以影响肿瘤微环境中的免疫细胞，这可能对免疫疗法的临床反应有益。
因此，联合表观遗传学和免疫疗法进行调节可能是提高该疗法成功的有前途的治疗选择。需要进一步的研究来：（1）深入了解表观遗传机制在肿瘤微环境中的影响；（2）根据肿瘤类型调节表观遗传机制以增加对免疫疗法的反应；（3）找到可靠的生物标志物，以便更好地选择适合免疫疗法的患者。
