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肿瘤免疫中RNA修饰的新见解:预防肿瘤免疫逃逸的有前景的靶点。

Novel insight into RNA modifications in tumor immunity: Promising targets to prevent tumor immune escape.

作者信息

Kong Yuxin, Yu Jie, Ge Shengfang, Fan Xianqun

机构信息

Department of Ophthalmology, Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200001, China.

出版信息

Innovation (Camb). 2023 May 29;4(4):100452. doi: 10.1016/j.xinn.2023.100452. eCollection 2023 Jul 10.

Abstract

An immunosuppressive state is a typical feature of the tumor microenvironment. Despite the dramatic success of immune checkpoint inhibitor (ICI) therapy in preventing tumor cell escape from immune surveillance, primary and acquired resistance have limited its clinical use. Notably, recent clinical trials have shown that epigenetic drugs can significantly improve the outcome of ICI therapy in various cancers, indicating the importance of epigenetic modifications in immune regulation of tumors. Recently, RNA modifications (N-methyladenosine [mA], N-methyladenosine [mA], 5-methylcytosine [mC], etc.), novel hotspot areas of epigenetic research, have been shown to play crucial roles in protumor and antitumor immunity. In this review, we provide a comprehensive understanding of how mA, mA, and mC function in tumor immunity by directly regulating different immune cells as well as indirectly regulating tumor cells through different mechanisms, including modulating the expression of immune checkpoints, inducing metabolic reprogramming, and affecting the secretion of immune-related factors. Finally, we discuss the current status of strategies targeting RNA modifications to prevent tumor immune escape, highlighting their potential.

摘要

免疫抑制状态是肿瘤微环境的典型特征。尽管免疫检查点抑制剂(ICI)疗法在防止肿瘤细胞逃避免疫监视方面取得了巨大成功,但原发性和获得性耐药限制了其临床应用。值得注意的是,最近的临床试验表明,表观遗传药物可以显著改善ICI疗法在各种癌症中的疗效,这表明表观遗传修饰在肿瘤免疫调节中的重要性。最近,RNA修饰(N-甲基腺苷[mA]、N-甲基腺苷[mA]、5-甲基胞嘧啶[mC]等)作为表观遗传研究的新热点领域,已被证明在促肿瘤和抗肿瘤免疫中发挥关键作用。在这篇综述中,我们全面了解了mA、mA和mC如何通过直接调节不同免疫细胞以及通过不同机制间接调节肿瘤细胞在肿瘤免疫中发挥作用,这些机制包括调节免疫检查点的表达、诱导代谢重编程以及影响免疫相关因子的分泌。最后,我们讨论了针对RNA修饰以防止肿瘤免疫逃逸的策略的现状,突出了它们的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd7c/10362524/b1b2a853b134/fx1.jpg

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