@article{d9c9558d1e6744daa659a41ce88104dd,
title = "MiR-130a and miR-145 reprogram Gr-1+CD11b+ myeloid cells and inhibit tumor metastasis through improved host immunity",
abstract = "Tumor-derived soluble factors promote the production of Gr-1+CD11b+ immature myeloid cells, and TGFβ signaling is critical in their immune suppressive function. Here, we report that miR-130a and miR-145 directly target TGFβ receptor II (TβRII) and are down-regulated in these myeloid cells, leading to increased TβRII. 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 IFNγ-producing cytotoxic CD8 T lymphocytes. miR-130a- and miR-145-targeted molecular networks including TGFβ 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.",
author = "Hiroki Ishii and Vodnala, {Suman K.} and Achyut, {Bhagelu Ram} and So, {Jae Young} and Hollander, {M. Christine} and Greten, {Tim F.} and Ashish Lal and Li Yang",
note = "Funding Information: The construct of 3'-UTR of T{\ss}RII luciferase reporter is a kind gift from Drs Nakashima, & Tariq Rana, Sanford-Burnham Medical Research Institute, and University of California San Diego School of Medicine. We thank Dr. Thomas Sayers in Cancer Inflammation Program, CCR, NCI to share 4T1.2 cell line overexpressing HA. We thank Dr. Yanli Pang for critical reading of the manuscript. We thank all staff in FACS Core for technical assistance. We are grateful for advice from Dr. Anand Merchant in bioinformatics analysis. This work was supported by NCI intramural funding to Dr. Li Yang. Funding Information: The construct of 3′-UTR of TβRII luciferase reporter is a kind gift from Drs Nakashima, & Tariq Rana, Sanford-Burnham Medical Research Institute, and University of California San Diego School of Medicine. We thank Dr. Thomas Sayers in Cancer Inflammation Program, CCR, NCI to share 4T1.2 cell line overexpressing HA. We thank Dr. Yanli Pang for critical reading of the manuscript. We thank all staff in FACS Core for technical assistance. We are grateful for advice from Dr. Anand Merchant in bioinformatics analysis. This work was supported by NCI intramural funding to Dr. Li Yang. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-05023-9",
language = "English (US)",
volume = "9",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
