Identification and characterization of B220+/B220− subpopulations in murine Gr1+CD11b+ cells during tumorigenesis

Abstract

ABSTRACT Although all murine MDSCs are defined as Gr1+CD11b+, their true immunophenotype remains elusive. In this study, we found murine Gr1+CD11b+ cells can be divided into two subsets: Gr1+CD11b+B220− and Gr1+CD11b+B220+, especially in the spleen tissues. Unlike the dominant B220− subset, the B220+ subpopulation was not induced by tumor in vivo. Moreover, Gr1+CD11b+B220+ cells from tumor-bearing mice spleens were unable to induce arginase 1 and inducible nitric oxide synthase expression, inhibit T cell proliferation, or promote tumor growth in primary tumor site. Nevertheless, these cells suppressed tumor metastasis in vivo and reduced cancer cell motility in vitro, while Gr1+CD11b+B220− cells from tumor-bearing mice spleens promoted tumor metastasis and enhanced cancer cell motility. Furthermore, both the polymorphonuclear (PMN-MDSCs) and monocytic MDSCs (Mo-MDSCs) could be further divided into B220− and B220+ subsets; interestingly, tumor only induced the expansion of B220− PMN-MDSCs and B220− Mo-MDSCs, but not the B220+ counterparts. Compared with B220− PMN-MDSCs and B220− Mo-MDSCs, the Ly6G+Ly6C−CD11b+B220+ and Ly6G−Ly6C+CD11b+B220+ cells from tumor-bearing mice spleens exhibited a more mature phenotype without immunosuppressive activity. Additionally, IL-6 deficiency attenuated the tumor-induced accumulation of MDSCs, B220− MDSCs and B220− PMN-MDSCs but increased the percentages of Gr1+CD11b+B220+, Ly6G+Ly6C−CD11b+B220+, and Ly6G−Ly6C+CD11b+B220+ cells, indicating the opposing roles of the IL-6 signaling pathway in the expansion of B220− MDSCs and their B220+ counterparts. Taken together, our findings indicate that the B220+ subset is a distinct subset of Gr1+CD11b+ cells functionally different from the B220− subpopulation during tumorigenesis and induction of MDSCs to B220+ cells may be helpful for cancer therapy.