Healthy myeloid-derived suppressor cells express the surface ectoenzyme Vanin-2 (VNN2)

Abstract

Study of human monocytic Myeloid-Derived Suppressor cells Mo-MDSC (CD14⁺ HLA-DR^neg/low) has been hampered by the lack of positive cell-surface markers. In order to identify positive markers for Mo-MDSC, we performed microarray analysis comparing Mo-MDSC cells from healthy subjects versus CD14⁺ HLA-DR^high monocytes. We have identified the surface ectoenzyme Vanin-2(VNN2) protein as a novel biomarker highly-enriched in healthy subjects Mo-MDSC. Indeed, healthy subjects Mo-MDSC cells expressed 68 % VNN2, whereas only 9% VNN2 expression was observed on CD14⁺ HLA-DR^high cells (n = 4 p < 0.01). The top 10 percent positive VNN2 monocytes expressed CD33 and CD11b while being negative for HLA-DR, CD3, CD15, CD19 and CD56, consistent with a Mo-MDSC phenotype. CD14⁺VNN2^high monocytes were able to inhibit CD8 T cell proliferation comparably to traditional Mo-MDSC at 51 % and 48 % respectively. However, VNN2 expression on CD14⁺ monocytes from glioma patients was inversely correlated to their grade. CD14⁺VNN2^high monocytes thus appear to mark a monocytic population similar to Mo-MDSC only in healthy subjects, which may be useful for tumor diagnoses.

Keywords: GPI-80; Immunosuppression; Mo-MDSC; VNN2.