期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-05023-9
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资金
- NCI
Tumor-derived soluble factors promote the production of Gr-1(+)CD11b(+) immature myeloid cells, and TGF beta signaling is critical in their immune suppressive function. Here, we report that miR-130a and miR-145 directly target TGF beta receptor II (T beta RII) and are down-regulated in these myeloid cells, leading to increased T beta RII. Ectopic expression of miR-130a and miR-145 in the myeloid cells decreased tumor metastasis. This is mediated through a downregulation of type 2 cytokines in myeloid cells and an increase in IFN gamma-producing cytotoxic CD8 T lymphocytes. miR-130a- and miR-145-targeted molecular networks including TGF beta and IGF1R pathways were correlated with higher tumor stages in cancer patients. Lastly, miR-130a and miR-145 mimics, as well as IGF1R inhibitor NT157 improved anti-tumor immunity and inhibited metastasis in preclinical mouse models. These results demonstrated that miR-130a and miR-145 can reprogram tumor-associated myeloid cells by altering the cytokine milieu and metastatic microenvironment, thus enhancing host antitumor immunity.
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