RNA m^(6)A修饰对髓源性抑制细胞的调控作用

The Regulation of RNA m^(6)A Modification on Myeloid-derived Suppressor Cells

RNA N^(6)-甲基腺苷(N^(6)-methyladenosine,m^(6)A)修饰主要受m^(6)A甲基转移酶、m^(6)A去甲基化酶和m^(6)A结合蛋白的调控,可以改变基因转录,从而调节生理和病理过程。近年来,越来越多的证据表明,m^(6)A甲基化在调节肿瘤微环境(tumor microenvironment,TME)中发挥至关重要作用,影响各种癌症的发生、发展和转移过程。髓源性抑制细胞(myeloid-derived suppressor cell,MDSC)为一群病理激活的未成熟髓系细胞,是TME中的重要免疫细胞。其主要通过抑制T细胞的活性发挥作用,从而促进恶性肿瘤的免疫逃逸。研究表明,靶向MDSC能够重塑免疫抑制微环境,提高癌症免疫治疗的疗效,是一种新的、有希望的免疫治疗靶点。m^(6)A修饰在一些免疫细胞的激活、分化和效应功能等方面的作用已受到广泛关注,但是m^(6)A修饰如何影响MDSC的研究仍非常有限,因此,进一步探讨二者之间的关系显得尤为重要。本综述在介绍MDSC及RNA m^(6)A修饰的基础上,总结了RNA m^(6)A修饰调控TME中MDSC的机制及研究进展,以期从表观调控的角度为靶向MDSC提供治疗肿瘤的新策略。

RNA m^(6)A modification is mainly regulated by m^(6)A methyltransferase,m^(6)A demethylase and m^(6)A binding protein,which can change gene transcription and thus regulating physiological and pathological processes.In recent years,more and more evidences have shown that m^(6)A methylation plays an important role in the regulation of tumor microenvironment(TME).It can affect the occurrence,development and metastasis of various types of cancer.Myeloid-derived suppressor cells(MDSCs),a group of immature myeloid cells,are important immune cells in TME which can be pathologically activated.It mainly inhibits the activity of T cells,so as to promote the immune escape of malignant tumors.Studies have shown that MDSC,a new and promising target for immunotherapy,can reshape the immunosuppressive microenvironment and modulate the efficacy of cancer immunotherapy.The role of m^(6)A modification in the activation,differentiation and effector function of some immune cells has been widely concerned.However,the research on how m^(6)A modification affects MDSC is still very limited.Therefore,it is particularly important to further explore the relationship between them.Based on the introduction of MDSC and RNA m^(6)A modification,this review summarizes the mechanism and research progress of RNA m^(6)A modification in regulating MDSC in TME in order to provide new strategies for targeting MDSC from the perspective of epigenetic modification.