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Epigenetic regulation of immunosuppressive tumor-associated macrophages through dysregulated microRNAs
Seminars in Cell & Developmental Biology ( IF 7.3 ) Pub Date : 2021-09-21 , DOI: 10.1016/j.semcdb.2021.09.001
Aamir Ahmad 1
Affiliation  

Macrophages are immune cells that play different roles under different physiological conditions. They are present in all tissues where they primarily protect from bacteria and pathogens in addition to assisting in tissue repair. During tumor progression, macrophages can exert contrasting effects based on the M1 vs. M2 polarization. The M2 macrophages support tumor growth through mechanisms that help suppress immune responses and/or circumvent immune-surveillance. A number of such mechanisms such as production of IL-10 and arginase, and expression of PD-L1, V-domain Ig suppressor of T cell activation and B7 family molecule B7-H4 are now believed central to the immunosuppressive effects of tumor-associated macrophages (TAMs). Emerging data has identified epigenetic regulation of these immunosuppressive mechanisms by small non-coding RNAs, the microRNAs (miRNAs). This review discusses the available literature on the subject, including the exosomes mediated transfer of miRNAs between cancer cells and the macrophages within the tumor microenvironment. A number of miRNAs are now believed to be involved in TAMs’ production of IL-10 and expression of PD-L1 while the information on such regulation of other immunosuppressive mechanisms is slowly emerging. A better understanding of epigenetic regulation of macrophages-mediated immunosuppressive effect can help identify novel targets for therapy and aid the design of future studies aimed at sensitizing tumors to immune responses.



中文翻译:

通过失调的微小RNA对免疫抑制性肿瘤相关巨噬细胞的表观遗传调控

巨噬细胞是在不同生理条件下发挥不同作用的免疫细胞。它们存在于所有组织中,除了帮助组织修复外,它们主要保护免受细菌和病原体的侵害。在肿瘤进展期间,巨噬细胞可以根据 M1 与 M2 极化发挥对比作用。M2 巨噬细胞通过有助于抑制免疫反应和/或规避免疫监视的机制来支持肿瘤生长。许多此类机制,例如 IL-10 和精氨酸酶的产生,以及 PD-L1、T 细胞活化的 V 域 Ig 抑制因子和 B7 家族分子 B7-H4 的表达,现在被认为是肿瘤相关免疫抑制作用的核心。巨噬细胞 (TAM)。新兴数据已经确定了小型非编码 RNA 对这些免疫抑制机制的表观遗传调控,微小RNA(miRNA)。本综述讨论了关于该主题的现有文献,包括外泌体介导的 miRNA 在癌细胞和肿瘤微环境中的巨噬细胞之间的转移。现在认为许多 miRNA 参与 TAM 的 IL-10 产生和 PD-L1 的表达,而有关其他免疫抑制机制的这种调节的信息正在慢慢出现。更好地了解巨噬细胞介导的免疫抑制作用的表观遗传调控有助于确定新的治疗靶点,并有助于设计旨在使肿瘤对免疫反应敏感的未来研究。现在认为许多 miRNA 参与 TAM 的 IL-10 产生和 PD-L1 的表达,而有关其他免疫抑制机制的这种调节的信息正在慢慢出现。更好地了解巨噬细胞介导的免疫抑制作用的表观遗传调控有助于确定新的治疗靶点,并有助于设计旨在使肿瘤对免疫反应敏感的未来研究。现在认为许多 miRNA 参与 TAM 的 IL-10 产生和 PD-L1 的表达,而有关其他免疫抑制机制的这种调节的信息正在慢慢出现。更好地了解巨噬细胞介导的免疫抑制作用的表观遗传调控有助于确定新的治疗靶点,并有助于设计旨在使肿瘤对免疫反应敏感的未来研究。

更新日期:2021-09-21
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