收稿日期: 2023-09-06
录用日期: 2024-04-18
网络出版日期: 2024-01-28
基金资助
上海市自然科学基金(21ZR1448700);上海交通大学医学院“双百人”项目(20191831)
Research progress of m6A methylation modification in regulating tumor immunity
Received date: 2023-09-06
Accepted date: 2024-04-18
Online published: 2024-01-28
Supported by
Shanghai Natural Science Foundation(21ZR1448700);"Two-hundred Talents" Program of Shanghai Jiao Tong University School of Medicine(20191831)
N6-甲基腺苷（N6-methyladenosine，m6A）是一种调控真核细胞基因表达最常见的修饰方式，影响RNA的剪接、降解、稳定性以及蛋白翻译等过程。研究表明m6A甲基化修饰与肿瘤发生发展密切相关，在肿瘤免疫应答的相关过程中也发挥着重要的调控作用。m6A修饰参与调节免疫细胞的分化、成熟过程以及相关的抗肿瘤免疫反应。在肿瘤微环境中，m6A修饰也可影响免疫细胞的募集、活化和极化等，从而促进或抑制肿瘤细胞的增殖与转移，起到重塑肿瘤免疫微环境的重要作用。近年来肿瘤的免疫治疗逐渐应用于临床，如免疫检查点抑制剂治疗、过继性细胞免疫治疗等，都取得了较好的临床效果。通过靶向m6A修饰来干预机体免疫系统，如通过小分子抑制剂靶向失调的m6A调控因子、诱导免疫细胞重编程等，可提高抗肿瘤免疫反应，加强免疫细胞对肿瘤细胞的识别和杀伤能力。m6A修饰是肿瘤免疫治疗的一个新方向，具有潜在的临床应用价值。该文围绕m6A甲基化修饰对免疫细胞及肿瘤免疫应答的调控作用进行综述，探讨其免疫治疗的新思路。
周海霞 , 张靖 . m6A甲基化修饰调控肿瘤免疫的研究进展[J]. 上海交通大学学报（医学版）, 2024 , 44(1) : 137 -144 . DOI: 10.3969/j.issn.1674-8115.2024.01.016
N6-methyladenosine (m6A) is the most prevalent modification that regulates gene expression in eukaryotes. It regulates splicing, degradation, stability, and translation of RNA. Numerous studies have demonstrated the close association between m6A methylation and tumor development, highlighting its crucial role in regulating tumor immune response. The m6A modification actively participates in governing immune cell differentiation and maturation as well as modulating anti-tumor immune responses. Within the tumor microenvironment, m6A modification can also impact the recruitment, activation, and polarization of immune cells, thereby either promoting or inhibiting tumor cell proliferation and metastasis. Consequently, it plays a pivotal role in reshaping the tumor immune microenvironment. In recent years, immunotherapy for tumors has been increasingly applied to clinical practice with notable success achieved through approaches such as immune checkpoint inhibitor therapy and adoptive cell immunotherapy. Targeting m6A modifications to interfere with the immune system, such as targeting dysregulated m6A regulators through small molecule inhibitors and inducing immune cell reprogramming, can improve anti-tumor immune response and strengthen immune cells′ ability to recognize and kill tumor cells. The m6A modification represents a novel avenue for potential clinical application within tumor immunotherapy. This review provides a comprehensive summary of the regulatory impact of m6A methylation modification on immune cells in the context of cancer, while also delving into novel targets for tumor immunotherapy.
Key words： m6A methylation; tumor immunity; immunotherapy
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