2. Academic Validation
  3. miR-130a and miR-145 reprogram Gr-1+CD11b+ myeloid cells and inhibit tumor metastasis through improved host immunity

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

  • Nat Commun. 2018 Jul 4;9(1):2611. doi: 10.1038/s41467-018-05023-9.
Hiroki Ishii 1,  Suman K Vodnala 1,  Bhagelu R Achyut 1 2,  Jae Young So 1,  M Christine Hollander 1,  Tim F Greten 3,  Ashish Lal 4,  Li Yang 5
Affiliations

Affiliations

  • 1 Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
  • 2 Tumor Angiogenesis Laboratory, Georgia Cancer Center, Augusta University, Augusta, 30912, USA.
  • 3 Gastrointestinal Malignancy Section, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
  • 4 Genetic Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
  • 5 Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA. yangl3@mail.nih.gov.
PMID: 29973593 DOI: 10.1038/s41467-018-05023-9
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z