Abstract
Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME) and are critical for cancer initiation and progression. MicroRNAs (miRNAs) could notably influence the phenotype of TAMs through various targets and signal pathways during cancer progression due to their post-transcriptional regulation. In this review, we discuss mainly the regulatory function of miRNAs on macrophage differentiation, functional polarization, and cellular crosstalk. Firstly, during the generation process, miRNAs take part in the differentiation from myeloid cells to mature macrophages, and this maturation process directly influences their recruitment into the TME, attracted by tumor cells. Secondly, macrophages in the TME can be either tumor-promoting or tumor-suppressing, depending on their functional polarization. Large numbers of miRNAs can influence the polarization of macrophages, which is crucial for tumor progression, including tumor cell invasion, intravasation, extravasation, and premetastatic site formation. Thirdly, crosstalk between tumor cells and macrophages is essential for TME formation and tumor progression, and miRNAs can be the mediator of communication in different forms, especially when encapsulated in microvesicles or exosomes. We also assess the potential value of certain macrophage-related miRNAs (MRMs) as diagnostic and prognostic markers, and discuss the possible development of MRM-based therapies.
概要
肿瘤相关巨噬细胞 (TAM) 是肿瘤微环境中比例最高的免疫细胞, 对肿瘤的发生和发展起着重要的作用. 在肿瘤的进展过程中, microRNA 可以通过转录后调控的方式作用于多种靶点与信号通路来影响 TAM 的表型. 本文主要讨论了 microRNA 对巨噬细胞分化、功能性极化和细胞间信息交流的调控作用. 首先, microRNA 参与了从髓样细胞向成熟巨噬细胞的分化过程, 这一过程直接影响了肿瘤微环境中肿瘤细胞对巨噬细胞的招募. 其次, microRNA 参与了 TAM 的功能极化, 使之表现为促癌或抑癌表型, 影响了肿瘤的生长和转移. 第三, 肿瘤细胞与巨噬细胞间的相互作用对肿瘤微环境的形成和肿瘤的进展而言是必要的, microRNA 可以通过胞外颗粒的形式作为交流的媒介. 此外, 本文还讨论了巨噬细胞相关 microRNA 作为肿瘤诊断和预后标志物的潜在价值, 以及基于巨噬细胞相关 microRNA 的肿瘤治疗新策略的应用前景.
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Chong CHEN and Jia-ming LIU wrote and edited the manuscript. Yun-ping LUO edited and checked the final version. All authors read and approved the final manuscript.
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Chong CHEN, Jia-ming LIU, and Yun-ping LUO declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
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Project supported by the National Natural Science Foundation of China (Nos. 81972795 and 1672914)
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Chen, C., Liu, Jm. & Luo, Yp. MicroRNAs in tumor immunity: functional regulation in tumor-associated macrophages. J. Zhejiang Univ. Sci. B 21, 12–28 (2020). https://doi.org/10.1631/jzus.B1900452
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DOI: https://doi.org/10.1631/jzus.B1900452