H3K4三甲基化调控癌症免疫:与免疫疗法结合的有希望的治疗靶点。
H3K4 trimethylation regulates cancer immunity: a promising therapeutic target in combination with immunotherapy.
发表日期:2023 Aug
作者:
Chu Xiao, Tao Fan, Yujia Zheng, He Tian, Ziqin Deng, Jingjing Liu, Chunxiang Li, Jie He
来源:
Journal for ImmunoTherapy of Cancer
摘要:
随着癌症免疫调控和免疫疗法的进展,对于组蛋白修饰在建立抗肿瘤免疫能力中的作用正在不断被揭示。开发涉及表观遗传药物(表观遗传药物)和免疫检查点阻断或嵌合抗原受体T细胞疗法的联合治疗有望提高免疫疗法的益处。组蛋白H3赖氨酸4三甲基化(H3K4me3)是肿瘤免疫调控中关键的表观遗传修饰,深度参与调节肿瘤免疫原性、重塑肿瘤免疫微环境和调节免疫细胞功能。然而,如何整合这些理论基础以构建基于H3K4三甲基化的新型治疗策略,并优化现有治疗仍然存在不确定性。本综述探讨了H3K4me3及其调节因子在抗肿瘤免疫中的机制,并探索了H3K4me3相关药物与免疫疗法结合治疗的潜力。深入理解H3K4me3在癌症免疫中的作用将有助于开发新型表观遗传治疗,并促进基于免疫疗法的联合方案的发展。© 作者(或其雇主)2023。在CC BY-NC下许可再使用。不得进行商业再使用。已由BMJ出版。
With the advances in cancer immunity regulation and immunotherapy, the effects of histone modifications on establishing antitumor immunological ability are constantly being uncovered. Developing combination therapies involving epigenetic drugs (epi-drugs) and immune checkpoint blockades or chimeric antigen receptor-T cell therapies are promising to improve the benefits of immunotherapy. Histone H3 lysine 4 trimethylation (H3K4me3) is a pivotal epigenetic modification in cancer immunity regulation, deeply involved in modulating tumor immunogenicity, reshaping tumor immune microenvironment, and regulating immune cell functions. However, how to integrate these theoretical foundations to create novel H3K4 trimethylation-based therapeutic strategies and optimize available therapies remains uncertain. In this review, we delineate the mechanisms by which H3K4me3 and its modifiers regulate antitumor immunity, and explore the therapeutic potential of the H3K4me3-related agents combined with immunotherapies. Understanding the role of H3K4me3 in cancer immunity will be instrumental in developing novel epigenetic therapies and advancing immunotherapy-based combination regimens.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.