Myeloid Derived Suppressor Cells(Mdscs) Emergence From Distinct Splenic Precursors

Abstract Myeloid derived suppressor cells(MDSCs) are a heterogenous population of immature myeloid cells, which accumulate in various pathological conditions, especially in tumor. In mice, MDSCs are characterized by the co-expression of Gr1 and CD11b molecules, and these cells could be classified into two subsets, CD11b+Ly6G+Ly6Clow polymorphonuclear neutrophil-like(PMN) MDSCs and CD11b+Ly6G-Ly6Chigh monocytic(Mo) MDSCs, by their expression of Ly6C and Ly6G molecules. Functional characteristics and fate of MDSCs are defined quite well. On the other hands, accumulation mechanism and origins of MDSC need to be more elucidated, and have not been fully understood whether MDSC could be generated in the periphery from distinct precursors in tumor microenvironment. For the first time, we identified the presence of splenic MDSC precursors in tumor bearing mice, characterized by CD11b+Ly6G-Ly6Cneg/low. We demonstrated that cytokines related to MDSC accumulation convert CD11b+Ly6G-Ly6Cneg/low cells into CD11b+Ly6G+Ly6Clow PMN-MDSC and/or CD11b+Ly6G-Ly6Chigh Mo-MDSC. These converted cells exerted strong suppressive activity on DO11.10 Tg splenocytes proliferation. Thus, these data suggest that there are peripheral distinct precursors, CD11b+Ly6Cneg/low cells, from which immunosuppressive MDSC could be generated.