title: Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice.
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.
authors.affiliation: H. Lee Moffitt Cancer Center, Tampa, Florida 33612, USA.
authors.forename: Je-In
authors.initials: JI
authors.lastname: Youn
authors.forename: Michelle
authors.initials: M
authors.lastname: Collazo
authors.forename: Irina N
authors.initials: IN
authors.lastname: Shalova
authors.forename: Subhra K
authors.initials: SK
authors.lastname: Biswas
authors.forename: Dmitry I
authors.initials: DI
authors.lastname: Gabrilovich
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006098:Granulocytes / Q000166:cytology / Q000276:immunology*; D016130:Immunophenotyping / Q000379:methods; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D013945:Thymoma / Q000276:immunology* / Q000473:pathology; D013953:Thymus Neoplasms / Q000276:immunology* / Q000473:pathology