Kumar R Ilaya, Jain Kavya, Rai Karan Raj, Gururajan Harshnna, Sarkar Koustav
Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India.
Immunol Res. 2025 Aug 19;73(1):121. doi: 10.1007/s12026-025-09678-7.
The field of epigenetics has significantly advanced our understanding of gene regulation in cancer, revealing dynamic modifications that do not alter the DNA sequence yet profoundly influence gene expression. These include DNA methylation, histone modifications, non-coding RNAs, chromatin remodeling, and RNA modifications. In malignancies such as colorectal, breast, lung, glioblastoma, and hematologic cancers, these epigenetic alterations contribute to tumor initiation, progression, and immune evasion. Emerging evidence reveals that such modifications shape the tumor-immune interface by influencing antigen presentation, immune cell infiltration, and cytokine signaling. This review explores the interplay between key epigenetic modifications and cancer immunity, emphasizing how these mechanisms contribute to immune escape and therapeutic resistance. We also examine the emergence of epigenetic therapies-particularly DNMT inhibitors, HDAC inhibitors, and BET inhibitors-as promising tools to reprogram immune responses and restore anti-tumor immunity. Furthermore, we discuss combinatorial approaches integrating epigenetic modulators with immune checkpoint inhibitors, underscoring their potential to enhance treatment efficacy. By outlining current challenges and emerging strategies, this review underscores the need for personalized epigenetic interventions and biomarker-driven approaches to improve outcomes in cancer immunotherapy. These insights establish epigenetic regulation as a critical frontier in next-generation cancer immunotherapy.
表观遗传学领域极大地推进了我们对癌症中基因调控的理解，揭示了动态修饰，这些修饰虽不改变DNA序列，但却深刻影响基因表达。这些修饰包括DNA甲基化、组蛋白修饰、非编码RNA、染色质重塑和RNA修饰。在结直肠癌、乳腺癌、肺癌、胶质母细胞瘤和血液系统癌症等恶性肿瘤中，这些表观遗传改变促进肿瘤的起始、进展和免疫逃逸。新出现的证据表明，此类修饰通过影响抗原呈递、免疫细胞浸润和细胞因子信号传导塑造肿瘤免疫界面。本综述探讨了关键表观遗传修饰与癌症免疫之间的相互作用，强调了这些机制如何导致免疫逃逸和治疗抵抗。我们还研究了表观遗传疗法的出现，特别是DNA甲基转移酶抑制剂、组蛋白去乙酰化酶抑制剂和溴结构域和额外末端结构域抑制剂，它们是重新编程免疫反应和恢复抗肿瘤免疫的有前景的工具。此外，我们讨论了将表观遗传调节剂与免疫检查点抑制剂相结合的联合方法，强调了它们提高治疗效果的潜力。通过概述当前的挑战和新出现的策略，本综述强调了个性化表观遗传干预和生物标志物驱动方法对于改善癌症免疫治疗结果的必要性。这些见解将表观遗传调控确立为下一代癌症免疫治疗的关键前沿领域。
