MiR-130a and miR-145 reprogram Gr-1+CD11b+ myeloid cells and inhibit tumor metastasis through improved host immunity

Hiroki Ishii, Suman K. Vodnala, Bhagelu Ram Achyut, Jae Young So, M. Christine Hollander, Tim F. Greten, Ashish Lal, Li Yang

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Article number2611
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

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immunity
metastasis
Myeloid Cells
Tumors
Immunity
tumors
Neoplasm Metastasis
cells
Neoplasms
Cytokines
T-cells
lymphocytes
inhibitors
Cytotoxic T-Lymphocytes
mice
cancer
Down-Regulation

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Ishii, H., Vodnala, S. K., Achyut, B. R., So, J. Y., Hollander, M. C., Greten, T. F., ... Yang, L. (2018). MiR-130a and miR-145 reprogram Gr-1+CD11b+ myeloid cells and inhibit tumor metastasis through improved host immunity. Nature Communications, 9(1), [2611]. https://doi.org/10.1038/s41467-018-05023-9

MiR-130a and miR-145 reprogram Gr-1+CD11b+ myeloid cells and inhibit tumor metastasis through improved host immunity. / Ishii, Hiroki; Vodnala, Suman K.; Achyut, Bhagelu Ram; So, Jae Young; Hollander, M. Christine; Greten, Tim F.; Lal, Ashish; Yang, Li.

In: Nature Communications, Vol. 9, No. 1, 2611, 01.12.2018.

Research output: Contribution to journalArticle

Ishii, H, Vodnala, SK, Achyut, BR, So, JY, Hollander, MC, Greten, TF, Lal, A & Yang, L 2018, 'MiR-130a and miR-145 reprogram Gr-1+CD11b+ myeloid cells and inhibit tumor metastasis through improved host immunity', Nature Communications, vol. 9, no. 1, 2611. https://doi.org/10.1038/s41467-018-05023-9
Ishii, Hiroki ; Vodnala, Suman K. ; Achyut, Bhagelu Ram ; So, Jae Young ; Hollander, M. Christine ; Greten, Tim F. ; Lal, Ashish ; Yang, Li. / MiR-130a and miR-145 reprogram Gr-1+CD11b+ myeloid cells and inhibit tumor metastasis through improved host immunity. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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