Center for Epigenetics and Disease Prevention, Texas A&M Health, Houston, TX, 77030, USA.
Department of Cardiovascular Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200070, China.
Clin Epigenetics. 2024 Jun 24;16(1):83. doi: 10.1186/s13148-024-01698-8.
Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a pivotal role in immune surveillance, orchestrating the recognition and elimination of tumor cells by the immune system. However, the intricate regulation of MHC gene expression is susceptible to dynamic epigenetic modification, which can influence functionality and pathological outcomes.
By understanding the epigenetic alterations that drive MHC downregulation, insights are gained into the molecular mechanisms underlying immune escape, tumor progression, and immunotherapy resistance. This systematic review examines the current literature on epigenetic mechanisms that contribute to MHC deregulation in esophageal, gastric, pancreatic, hepatic and colorectal malignancies. Potential clinical implications are discussed of targeting aberrant epigenetic modifications to restore MHC expression and 0 the effectiveness of immunotherapeutic interventions.
The integration of epigenetic-targeted therapies with immunotherapies holds great potential for improving clinical outcomes in patients with gastrointestinal malignancies and represents a compelling avenue for future research and therapeutic development.
胃肠道恶性肿瘤包含了一组具有挑战性的癌症，对全球健康构成了重大威胁。主要组织相容性复合体（MHC）在免疫监视中起着关键作用，协调免疫系统识别和消除肿瘤细胞。然而，MHC 基因表达的复杂调控容易受到动态表观遗传修饰的影响，这可能会影响其功能和病理结果。
通过了解导致 MHC 下调的表观遗传改变，可以深入了解免疫逃逸、肿瘤进展和免疫治疗耐药的分子机制。本系统综述检查了目前关于导致食管、胃、胰腺、肝和结直肠恶性肿瘤中 MHC 失调的表观遗传机制的文献。讨论了针对异常表观遗传修饰以恢复 MHC 表达和免疫治疗效果的潜在临床意义。
将表观遗传靶向治疗与免疫治疗相结合，有望改善胃肠道恶性肿瘤患者的临床结局，是未来研究和治疗发展的一个有吸引力的途径。
