Tumor-Associated Myeloid-Derived Suppressor Cells

Abstract

This chapter describes the induction, characteristics, and the effector mechanisms of the myeloid-derived suppressor cells (MDSCs). It reviews the evidence demonstrating how their suppressive activity promotes tumor progression, and explores some of the strategies developed to eliminate this heterogeneous population of detrimental cells. The MDSCs have potent immunosuppressive activity and inhibit both the adaptive and innate immunity by preventing the activation of CD4+ and CD8+ T cells, by reducing the number of mature dendritic cells (DCs), by suppressing the natural killer (NK) cell cytotoxicity, and by skewing the immunity towards a type 2 phenotype—that is compatible with cancer. MDSCs mediate their suppressive activity mainly through multiple mechanisms, including the production of arginase and inducible nitric oxide synthase, the promotion of tumor angiogenesis, and the induction of regulatory T cells (Tregs). The tumor-secreted factors such as—the vascular endothelial growth factor (VEGF) and the granulocyte-macrophage colony-stimulating factor (GM-CSF), and a few proinflammatory mediators—induce the accumulation and retention of the MDSCs.