Format

Send to

Choose Destination
Immunity. 2016 Feb 16;44(2):303-15. doi: 10.1016/j.immuni.2016.01.014.

CD45 Phosphatase Inhibits STAT3 Transcription Factor Activity in Myeloid Cells and Promotes Tumor-Associated Macrophage Differentiation.

Author information

1
The Wistar Institute, Philadelphia, PA 19104, USA.
2
H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.
3
Thomas Jefferson University, Philadelphia, PA 19110, USA.
4
Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, DE 19713, USA.
5
University of Pennsylvania, Philadelphia, PA 19104, USA.
6
Indiana University School of Medicine, Indianapolis, IN 46202, USA.
7
The Wistar Institute, Philadelphia, PA 19104, USA. Electronic address: dgabrilovich@wistar.org.

Abstract

Recruitment of monocytic myeloid-derived suppressor cells (MDSCs) and differentiation of tumor-associated macrophages (TAMs) are the major factors contributing to tumor progression and metastasis. We demonstrated that differentiation of TAMs in tumor site from monocytic precursors was controlled by downregulation of the activity of the transcription factor STAT3. Decreased STAT3 activity was caused by hypoxia and affected all myeloid cells but was not observed in tumor cells. Upregulation of CD45 tyrosine phosphatase activity in MDSCs exposed to hypoxia in tumor site was responsible for downregulation of STAT3. This effect was mediated by the disruption of CD45 protein dimerization regulated by sialic acid. Thus, STAT3 has a unique function in the tumor environment in controlling the differentiation of MDSC into TAM, and its regulatory pathway could be a potential target for therapy.

PMID:
26885857
PMCID:
PMC4759655
DOI:
10.1016/j.immuni.2016.01.014
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center