Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150081, Heilongjiang, China.
Heilongjiang Academy of Medical Sciences, 157 Baojian Road, Harbin, 150086, Heilongjiang, China.
Mol Cancer. 2022 Sep 7;21(1):176. doi: 10.1186/s12943-022-01652-3.
Immunotherapy, especially immune checkpoint inhibitors (ICIs), has revolutionized the treatment of many types of cancer, particularly advanced-stage cancers. Nevertheless, although a subset of patients experiences dramatic and long-term disease regression in response to ICIs, most patients do not benefit from these treatments. Some may even experience cancer progression. Immune escape by tumor cells may be a key reason for this low response rate. N-methyladenosine (mA) is the most common type of RNA methylation and has been recognized as a critical regulator of tumors and the immune system. Therefore, mA modification and related regulators are promising targets for improving the efficacy of tumor immunotherapy. However, the association between mA modification and tumor immune escape (TIE) has not been comprehensively summarized. Therefore, this review summarizes the existing knowledge regarding mA modifications involved in TIE and their potential mechanisms of action. Moreover, we provide an overview of currently available agents targeting mA regulators that have been tested for their elevated effects on TIE. This review establishes the association between mA modifications and TIE and provides new insights and strategies for maximizing the efficacy of immunotherapy by specifically targeting mA modifications involved in TIE.
免疫疗法，特别是免疫检查点抑制剂（ICIs），已经彻底改变了许多类型癌症的治疗方法，特别是晚期癌症。然而，尽管一小部分患者对 ICI 治疗有明显和长期的疾病缓解，但大多数患者并未从中受益。一些患者甚至可能出现癌症进展。肿瘤细胞的免疫逃逸可能是这种低反应率的一个关键原因。N6-甲基腺苷（m6A）是最常见的 RNA 甲基化类型，已被认为是肿瘤和免疫系统的关键调节剂。因此，m6A 修饰及其相关调节剂是提高肿瘤免疫治疗效果的有前途的靶点。然而，m6A 修饰与肿瘤免疫逃逸（TIE）之间的关联尚未得到全面总结。因此，本综述总结了目前关于 TIE 中涉及的 m6A 修饰及其潜在作用机制的知识。此外，我们还概述了目前已测试过的针对 m6A 调节剂的可用药物，这些药物可提高 TIE 的效果。本综述建立了 m6A 修饰与 TIE 之间的联系，并为通过专门针对 TIE 中涉及的 m6A 修饰来最大限度地提高免疫疗法的疗效提供了新的见解和策略。
