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MicroRNA-22 represses glioma development via activation of macrophage-mediated innate and adaptive immune responses

Oncogene volume 41, pages 2444–2457 (2022)Cite this article

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A Correction to this article was published on 31 March 2022

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Abstract

Macrophage-mediated tumor cell phagocytosis and subsequent neoantigen presentation are critical for generating anti-tumor immunity. This study aimed to uncover the potential clinical value and molecular mechanisms of miRNA-22 (miR-22) in tumor cell phagocytosis via macrophages and more efficient T cell priming. We found that miR-22 expression was markedly downregulated in primary macrophages from glioma tissue samples compared to adjacent tissues. miR-22-overexpressing macrophages inhibited glioma cell proliferation and migration, respectively. miR-22 upregulation stimulated the phagocytic ability of macrophages, enhanced tumor cell phagocytosis, antigen presentation, and efficient T cell priming. Additionally, our data revealed that miR-22-overexpressing macrophages inhibited glioma formation in vivo, HDAC6 was a target, and NF-κB signaling was a pathway closely associated with miR-22 in tumor-associated macrophages (TAMs) of glioma. Our findings revealed the essential roles of miR-22 in tumor cell phagocytosis by macrophages and more efficient T cell priming, facilitating further research on phagocytic regulation to enhance the response to tumor immunotherapy.

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Fig. 1: miR-22 is downregulated in glioma tissues, as well as in tumor-infiltrating macrophages.
Fig. 2: miR-22-overexpressing macrophages indirectly inhibits glioma cells proliferation and migration.
Fig. 3: miR-22 enhances the phagocytic ability of macrophages.
Fig. 4: miR-22 increases the antigen presentation and CD8+ T cell priming in a NF-κB-dependent manner.
Fig. 5: miR-22-overexpressing macrophages inhibit glioma formation in vivo.
Fig. 6: HDAC6 is a target of miR-22 and HDAC6 deficiency mimics miR-22 overexpression-mediated anti-tumor effect in macrophages.
Fig. 7: Outline diagram of the anti-tumor effects of miR-22/HDAC6/NF-κB axis in macrophage of glioma.

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Funding

This study was supported by the National Natural Science Foundation of China (31900616, 81673444, 82003795), The project of improvement of the scientific ability of Anhui Medical University (2020xkjT009), Natural Science Foundation of Anhui Province for young scholars (1908085QH379) and The Open Fund of Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, P.R. China, Anhui Medical University (KFJJ-2021-01).

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  1. These authors contributed equally: Jiajie Tu, Yilong Fang

Authors and Affiliations

  1. Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, China

    Jiajie Tu, Yilong Fang, Dafei Han, Xuewen Tan, Zhen Xu, Haifeng Jiang & Wei Wei

  2. Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China

    Xinming Wang & Wenming Hong

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Contributions

JT and YF performed the experiments and drafted the manuscript. DH, XT, ZX, HJ, XW, WH, and WW revised the manuscript.

Corresponding authors

Correspondence to Wenming Hong or Wei Wei.

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The authors declare no competing interests.

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Patients with glioma were recruited from the First Affiliated Hospital of Anhui Medical University, approved by the Medicine Research Ethics Committee of Anhui Medical University. All glioma patients gave informed consent to relevant experimental protocols. All animal experiments were performed in accordance with the guidelines of the Institutional Laboratory Animal Care and Use Committee, Anhui Medical University.

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Tu, J., Fang, Y., Han, D. et al. MicroRNA-22 represses glioma development via activation of macrophage-mediated innate and adaptive immune responses. Oncogene 41, 2444–2457 (2022). https://doi.org/10.1038/s41388-022-02236-7

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