School of Postgraduate Studies, International Medical University, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.
State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Pudong New District, Shanghai, 200127, China.
Cell Biol Toxicol. 2023 Dec;39(6):2501-2526. doi: 10.1007/s10565-023-09830-9. Epub 2023 Sep 27.
Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer that is highly associated with Epstein-Barr virus (EBV) infection. EBV acts as an epigenetic driver in NPC tumorigenesis, reprogramming the viral and host epigenomes to regulate viral latent gene expression, and creating an environment conducive to the malignant transformation of nasopharyngeal epithelial cells. Targeting epigenetic mechanisms in pre-clinical studies has been shown promise in eradicating tumours and overcoming immune resistance in some solid tumours. However, its efficacy in NPC remains inclusive due to the complex nature of this cancer. In this review, we provide an updated understanding of the roles of epigenetic factors in regulating EBV latent gene expression and promoting NPC progression. We also explore the crosstalk between epigenetic mechanisms and immune evasion in NPC. Particularly, we discuss the potential roles of DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors in reversing immune suppression and augmenting antitumour immunity. Furthermore, we highlight the advantages of combining epigenetic therapy and immune checkpoint inhibitor to reverse immune resistance and improve clinical outcomes. Epigenetic drugs have the potential to modulate both epigenetic mediators and immune factors involved in NPC. However, further research is needed to fully comprehend the diverse range of epigenetic modifications in NPC. A deeper understanding of the crosstalk between epigenetic mechanisms and immune evasion during NPC progression is crucial for the development of more effective treatments for this challenging disease.
鼻咽癌(NPC)是一种独特的头颈部癌症,与 Epstein-Barr 病毒(EBV)感染高度相关。EBV 在 NPC 肿瘤发生中作为一种表观遗传驱动因素,重新编程病毒和宿主表观基因组以调节病毒潜伏基因表达,并创造有利于鼻咽上皮细胞恶性转化的环境。在一些实体瘤中,针对表观遗传机制的临床前研究已显示出在消除肿瘤和克服免疫抵抗方面的潜力。然而,由于这种癌症的复杂性,其在 NPC 中的疗效仍存在争议。在这篇综述中,我们提供了对表观遗传因素在调节 EBV 潜伏基因表达和促进 NPC 进展中的作用的最新理解。我们还探讨了表观遗传机制与 NPC 中免疫逃逸之间的串扰。特别是,我们讨论了 DNA 甲基转移酶(DNMT)和组蛋白去乙酰化酶(HDAC)抑制剂在逆转免疫抑制和增强抗肿瘤免疫方面的潜在作用。此外,我们强调了将表观遗传治疗与免疫检查点抑制剂相结合以逆转免疫抵抗和改善临床结果的优势。表观遗传药物有可能调节 NPC 中涉及的表观遗传介质和免疫因子。然而,需要进一步研究以充分了解 NPC 中不同类型的表观遗传修饰。深入了解 NPC 进展过程中表观遗传机制与免疫逃逸之间的串扰对于开发针对这种具有挑战性的疾病的更有效治疗方法至关重要。