MicroRNA-22 represses glioma development via activation of macrophage-mediated innate and adaptive immune responses
MicroRNA-22 represses glioma development via activation of macrophage-mediated innate and adaptive immune responses
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DOI：
10.1038/s41388-022-02236-7
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发表时间：
2022-03
期刊：
影响因子：
8
通讯作者：
Jiajie Tu;Yilong Fang;Dafei Han;Xuewen Tan;Zhen Xu;Hai-feng Jiang;Xinming Wang;Wenming Hong;Wei Wei-Wei
中科院分区：
文献类型：
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作者：
Jiajie Tu;Yilong Fang;Dafei Han;Xuewen Tan;Zhen Xu;Hai-feng Jiang;Xinming Wang;Wenming Hong;Wei Wei-Wei
巨噬细胞介导的肿瘤细胞吞噬作用和随后的新抗原呈递对于产生抗肿瘤免疫至关重要。本研究旨在揭示miRNA-22（miR-22）在巨噬细胞吞噬肿瘤细胞和更有效的T细胞引发中的潜在临床价值和分子机制。我们发现，与邻近组织相比，来自胶质瘤组织样品的原代巨噬细胞中miR-22表达显著下调。过表达miR-22的巨噬细胞分别抑制胶质瘤细胞增殖和迁移。miR-22上调刺激巨噬细胞的吞噬能力，增强肿瘤细胞的吞噬作用，抗原呈递和有效的T细胞引发。此外，我们的数据显示，miR-22过表达的巨噬细胞在体内抑制胶质瘤的形成，HDAC 6是一个靶点，NF-κB信号通路是与胶质瘤的肿瘤相关巨噬细胞（TAM）中的miR-22密切相关的通路。我们的研究结果揭示了miR-22在巨噬细胞吞噬肿瘤细胞和更有效的T细胞启动中的重要作用，促进了对吞噬调节的进一步研究，以增强对肿瘤免疫治疗的反应。
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.