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J Leukoc Biol. 2012 Jan;91(1):167-81. doi: 10.1189/jlb.0311177. Epub 2011 Sep 27.

Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice.

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1
H. Lee Moffitt Cancer Center, Tampa, Florida 33612, USA.

Abstract

MDSCs are a group of cells with potent immune-suppressive activity. These cells accumulate in many pathologic conditions and play a major role in the regulation of immune responses. The nature of MDSC remains highly debatable. In cancer, most MDSCs are represented by cells with granulocytic phenotype and morphology, G-MDSC. The relationship between G-MDSCs and Neu remains unclear. In this study, we have found that G-MDSCs, from tumor-bearing, and Neu, from tumor-free, mice share a common morphology and phenotype. However, in contrast to Neu, a substantial proportion of G-MDSCs expressed M-CSFR and a CD244 molecule. Neu had significantly higher phagocytic activity, expression of lysosomal proteins, and TNF-α than corresponding G-MDSCs, which had significantly higher activity of arginase, MPO, and ROS. In contrast to G-MDSC, neither rested nor mobilized Neu suppressed T cells. G-MDSC survived 2 days in culture in the presence of GM-CSF and within 24 h, became phenotypic and functionally similar to Neu. Tumor-associated G-MDSC shared most characteristics of splenic G-MDSC, rather then Neu. These data suggest that in cancer, despite morphological and phenotypic similarities, G-MDSCs are functionally distinct from Neu and are comprised of pathologically activated precursors of Neu.

PMID:
21954284
PMCID:
PMC3250305
DOI:
10.1189/jlb.0311177
[Indexed for MEDLINE]
Free PMC Article
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