Human myeloid derived suppressor cell (MDSC) subset phenotypes

Abstract

Abstract MDSCs are increased in cancer patients and were originally defined based on T-cell suppression and a negative correlation with prognosis and overall survival and a direct correlation with tumor stage. They were originally described, based on CD34 expression and a hematopoietic progenitor phenotype. However, their phenotypic definition is investigator dependent in association with suppressor cell function. There are two main subsets defined based on a lack of lymphoid and differential expression of myeloid markers resulting in a cellular continuum from multi-potential hematopoietic progenitors to differentiated granulocytes and monocytes. One recent hypothesis is that MDSCs form three subsets including macrophage MDSC (CD14+ and no CD15 or CD66b); granulocytic MDSCs (CD15 and/or CD66b expression and no CD14); and immature (i-) MDSC (linage (Lin) negative, CD33+ cells). Unfortunately, there is no consensus on markers extent to CD14 and CD15 with linage and HLA-DR negativity providing a frequent; although not universal theme. We report a flow cytometry gating strategy utilizing a single staining tube and a linear phenotypic characterization of MDSC subsets supported by density and T-cell suppression. We suggest that staining with antibodies to Lin, HLA-DR, CD14, CD15, CD11b and CD33 is sufficient to subset into the three phenotypes that can be further subset based on CD16. PDL1 and CD34 expression. The majority of iMDSC are CD34+CD33+ cells supporting a plastic phenotype and myeloid commitment and can be further, delineated based on CD16 expression supporting immaturity. We note, that some cancer patients express MDSCs at high levels; although the subsets preponderance varies between patients.