Host miR155 promotes tumor growth through a myeloid-derived suppressor cell-dependent mechanism

Siqi Chen, Long Wang, Jie Fan, Cong Ye, Donye Dominguez, Yi Zhang, Tyler J. Curiel, Deyu Fang, Timothy M. Kuzel, Bin Zhang

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

miR155 is a regulator of immune cell development and function that is generally thought to be immunostimulatory. However, we report here that genetic ablation of miR155 renders mice resistant to chemical carcinogenesis and the growth of several transplanted tumors, suggesting that miR155 functions in immunosuppression and tumor promotion. Host miR155 deficiency promoted overall antitumor immunity despite the finding of defective responses of miR155-deficient dendritic cells and antitumor T cells. Further analysis of immune cell compartments revealed that miR155 regulated the accumulation of functional myeloid-derived suppressive cells (MDSC) in the tumor microenvironment. Specifically, miR155 mediated MDSC suppressor activity through at least two mechanisms, including SOCS1 repression and a reduced ability to license the generation of CD4+Foxp3+ regulatory T cells. Importantly, we demonstrated that miR155 expression was required for MDSC to facilitate tumor growth. Thus, our results revealed a contextual function for miR155 in antitumor immunity, with a role in MDSC support that appears to dominate in tumor-bearing hosts. Overall, the balance of these cellular effects appears to be a root determinant of whether miR155 promotes or inhibits tumor growth.

Original languageEnglish (US)
Pages (from-to)519-531
Number of pages13
JournalCancer Research
Volume75
Issue number3
DOIs
StatePublished - Feb 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Host miR155 promotes tumor growth through a myeloid-derived suppressor cell-dependent mechanism'. Together they form a unique fingerprint.

  • Cite this

    Chen, S., Wang, L., Fan, J., Ye, C., Dominguez, D., Zhang, Y., Curiel, T. J., Fang, D., Kuzel, T. M., & Zhang, B. (2015). Host miR155 promotes tumor growth through a myeloid-derived suppressor cell-dependent mechanism. Cancer Research, 75(3), 519-531. https://doi.org/10.1158/0008-5472.CAN-14-2331