VNN2 is a new surface marker for monocytic human myeloid-derived suppressor cells (TUM4P.900)

Abstract

Abstract Studies of myeloid-derived suppressor cells (MDSC) have been hampered by the scarcity and lack of cell-specific markers. Specifically, monocytic MDSC (M-MDSC) are currently characterized as CD14+ HLA-DR-/low and only the absence or low expression of HLA-DR is used as a marker to specifically isolate and purify live M-MDSC. However, identifying cells based on the absence or reduce expression of a protein significantly hampers their study. Reviewing previous studies regarding monocytic markers, we noted Vanin-2 as a protein that has been described in the past to be present in monocytic subsets displaying reduced antigen presentation as well as high reactive oxygen production, hallmarks of MDSC. In order to determine if this marker was present on cells we currently classify as M-MDSC, we used flow cytometry to isolate MDSCs and compared by qPCR CD14+ HLA-DR-/low (M-MDSC) versus CD14+ HLA-DR+ monocytes for VNN2 expression. Interestingly VNN2 showed a 12.43 fold increase in CD14+ HLA-DR-/low M-MDSC compared to CD14+ HLA-DR+ monocytes. Next, we sorted CD14+ VNN2+-expressing monocytes (>10%) and we performed a suppressive assay with autologous bead-stimulated CD8 T-cells. This assay showed CD14+ VNN2+ monocytes suppressive capabilities were comparable to those of traditional CD14+ HLA-DR-/low M-MDSC at 24%, compared to CD8 T-cells alone (90%) or CD14+ VNN2neg monocytes (~70%). These results suggest VNN2 might be a viable surface marker to positively identify live human M-MDSC.