Abstract LB-192: Phenotyping human myeloid derived suppressor cells (MDSC) subsets

Abstract

Abstract MDSCs are heterogeneous occurring at varying stages of commitment and differentiation. They increase in cancer and other patients with inflammatory diseases and may best be defined based on their ability to suppress T and B cell responses. In recent years these cells have demonstrated clinical relevance, including a negative correlation with prognosis and overall survival in cancer patients increasing with tumor progression and stage. MDSCs were originally described in mice based on a lack of phenotypic markers, i.e. null cells, or predicated on their function, as natural suppressor (NS) cells. Subsequently they were found in humans, based on CD34 expression supporting a hematopoietic progenitor phenotype. The identification of human phenotype(s) is complicated by the association of suppressor cell function with multiple phenotypes. This includes two main subsets defined based on the expression or lack of myeloid and lymphoid markers, with specific phenotypes extent investigator dependent. There is a consensus that MDSCs constitute a continuum of immature to differentiated myeloid cells ranging from multi-potential hematopoietic progenitors to morphologically differentiated granulocytic and monocytic leukocytes. One trending hypothesis is that MDSC phenotypes form three subsets include macrophage (M-) MDSCs with a monocytic morphology, expressing CD14 and no CD15 or CD66b and granulocytic (G)-MDSCs phenotypically characterized by CD15 and/or CD66B expression and no CD14; and an immature (i-) MDSC defined as linage negative, CD33+ cells. Unfortunately, there is no consensus on markers extent to CD14 and CD15 although linage negative and DR- provide a common theme; although not commonly utilized between laboratories and MDSC subset. We provide herein a Flow cytometric strategy utilizing single staining tube and a linear phenotypic characterization that is supported by density and T-cell suppression confirmation. We suggest that staining with Lin, HLA-DR, CD14, CD15, CD11b, CD33 antibodies provides sufficient markers to subset into the three MDSC phenotypes that can be further subset with CD16. PDL1 and CD34 expression. Interestingly the majority of iMDSC express CD34 on the CD33+ cells together with CD14 or CD15 supporting a plastic phenotype with myeloid commitment. All subset can be further, delineated based on CD16 expression further suggesting immaturity. We will note, that some cancer patients express these cell phenotypes at very high levels in the circulation; although the preponderance of G-MDSC vs M-MDSC varies between patients. Citation Format: James E. Talmadge, Holly Britton, Alicia Dafferner, Phyllis Warkentin, Kathryn Cole. Phenotyping human myeloid derived suppressor cells (MDSC) subsets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-192. doi:10.1158/1538-7445.AM2017-LB-192