研究动态
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m6A介导的PD-1/PD-L1在抗肿瘤免疫中的作用。

The role of m6A-mediated PD-1/PD-L1 in antitumor immunity.

发表日期:2023 Feb 21
作者: Li Liu, Long Liang, Hui Li, Wenjun Shao, Chaoying Yang, Feng Lin, Jing Liu, Ji Zhang
来源: BIOCHEMICAL PHARMACOLOGY

摘要:

N6-甲基腺苷(m6A)是真核细胞内部后转录RNA修饰中最普遍、最丰富和最保守的一种类型。新兴证据表明,m6A修饰执行重要功能,影响抗肿瘤免疫力。程序性死亡因子1(PD-1)和程序性细胞死亡配体1(PD-L1)是最受关注的免疫检查点通路。PD-L1与其受体PD-1的相互作用抑制细胞毒性T细胞介导的肿瘤反应,通过阻断这种相互作用已被证明是各种癌症的有效免疫治疗策略。不幸的是,由于不确定的耐药性,很少有癌症患者从这两个工具中受益。 m6A在各种癌症中起着重要作用,影响RNA生物发生和过程。了解药物耐药性的分子机制将促进个性化临床管理的发展。在本文中,我们系统地讨论了m6A调节PD-1和PD-L1表达的机制,以及它们在肿瘤免疫治疗过程中的作用和m6A相关分子的潜在应用前景。此外,建立不断增长的m6Ascore以评估癌症的预后。版权所有©2023 Elsevier Inc.。保留所有权利。
N6-methyladenosine (m6A) is the most prevalent, abundant and conserved type of internal posttranscriptional RNA modification in eukaryotic cells. Emerging evidence suggests that m6A modifications perform important functions that affect antitumor immunity. Programmed death 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) are the two most well-studied immune checkpoint pathways. The interaction of PD-L1 with its receptor PD-1 inhibits cytotoxic T-cell-mediated tumor responses, and blockade of this interaction has proven to be an effective immunotherapy strategy in various cancers. Unfortunately, few cancer patients benefit from the two tools due to uncertain resistance. m6A plays an important role in affecting RNA biogenesis and process in various cancers. Understanding the molecular mechanism of drug resistance will promote the development of personalized clinical management. In this review, we systematically discussed the mechanisms by which m6A regulates PD-1 and PD-L1 expression and further their functions in the process of tumor immunotherapy and the potential application prospects of m6A-associated molecules. Moreover, mounting m6Ascore is established to evaluate the prognosis of cancer.Copyright © 2023 Elsevier Inc. All rights reserved.