Alteration of functionality and differentiation directed by changing gene expression patterns in myeloid derived suppressor cells (MDSCs) in tumor microenvironment and bone marrow through early to terminal phase of tumor progression.

Myeloid derived suppressor cells (MDSCs) are heterogenous immature myeloid lineage cells that can differentiate into neutrophils, monocytes and Dendritic cells as well (1, 2). These cells have been characterized to have potent immunosuppressive capacity in neoplasia and neoplastic chronic inflammatory microenvironment. Increased accumulation of MDSCs was reported with poor clinical outcomes in patients. They support neoplastic progression by abrogating antitumor immunity through inhibition of lymphocyte functions and directly by facilitating tumor development. Yet the shifting genetic signatures of this myeloid lineage cell towards immunosuppressive functionality in progressive tumor development remain elusive. We have attempted to identify the gene expression profile using lineage specific markers of these unique myeloid lineage cells in tumor microenvironment (TME) and bone marrow using liquid transplantable mice tumor model to trace the changing influence of TME on MDSCs. We analyzed the phenotype, functional shift, suppressive activity, differentiation status and microarray-based gene expression profile of CD11b+ Gr1+ lineage specific cells isolated from TME and bone marrow of four stages of tumor-bearing mice and compared them with control counterparts. Our analysis of differentially expressed genes of MDSCs isolated from bone marrow and TME reveals unique gene expression patterns in the bone marrow and TME-derived MDSCs. It also suggests T cell suppressive activity of MDSCs progressively increases toward mid to late phase of the tumor and a significant differentiation bias of tumor site MDSCs towards macrophage even in presence of differentiating agents indicating potential molecular characteristics of MDSCs in different stages of tumor that can emerge as intervention target.