肥胖与癌症:一项转化科学综述
Obesity and Cancer: A Translational Science Review.
超重和肥胖与更高的癌症发病率相关,在美国每年占新发癌症诊断的 10%。减重可能通过减轻肥胖的不良影响来降低癌症风险,但可能需要减重超过 10% 才能降低癌症风险。
英文原题:Epigenetic regulation in gynecological cancers: a paradigm shift in immunotherapy strategies.
Epigenetic regulation in gynecological cancers: a paradigm shift in immunotherapy strategies.
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近年来,免疫治疗的进展已改变妇科肿瘤的治疗格局;然而,由于肿瘤异质性和免疫逃逸机制,持久缓解仍然有限。新出现的证据强调,表观遗传修饰,包括DNA甲基化、组蛋白修饰和RNA甲基化,是肿瘤免疫微环境和免疫治疗疗效的关键调控因素。本综述全面探讨了这些表观遗传改变如何在宫颈癌、卵巢癌和子宫内膜癌中调节免疫细胞浸润、抗原呈递、免疫检查点表达和肿瘤免疫原性。
我们还描述了特定表观遗传酶,如DNMTs、HDACs、BET和RNA甲基转移酶,在塑造免疫反应中的作用,并讨论了靶向这些调控因子以使肿瘤对免疫检查点抑制剂、癌症疫苗、基于细胞因子的治疗和过继性T细胞治疗敏感的潜在治疗价值。
此外,我们审视了表观遗传药物如DNMT和HDAC抑制剂与免疫治疗在临床前和临床环境中的整合,强调其克服免疫耐受的协同能力。通过阐明表观遗传调控与免疫动态之间的相互作用,本综述强调了一种向精准免疫表观遗传策略的范式转变,为改善妇科恶性肿瘤的治疗结局提供了一个有前景的框架。
Recent advances in immunotherapy have transformed the therapeutic landscape of gynecological cancers; however, durable responses remain limited by tumor heterogeneity and immune evasion mechanisms. Emerging evidence highlights epigenetic modifications comprising of DNA methylation, histone modifications, and RNA methylation as pivotal regulators of the tumor immune microenvironment and immunotherapy efficacy.
This review comprehensively explores how these epigenetic alterations modulate immune cell infiltration, antigen presentation, immune checkpoint expression, and tumor immunogenicity across cervical, ovarian, and endometrial cancers.
We also delineate the impact of specific epigenetic enzymes, such as DNMTs, HDACs, BET and RNA methyltransferases, in shaping immune responses and discuss the therapeutic potential of targeting these regulators to sensitize tumors to immune checkpoint inhibitors, cancer vaccines, cytokine based treatments and adoptive T-cell therapies.
Furthermore, we examine the integration of epigenetic agents such as DNMT and HDAC inhibitors with immunotherapies in preclinical and clinical settings, emphasizing their synergistic capacity to overcome immunoresistance. By illuminating the interplay between epigenetic regulation and immune dynamics, this review underscores a paradigm shift toward precision immunoepigenetic strategies, offering a promising framework for enhancing therapeutic outcomes in gynecological malignancies.
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