Immunomodulatory effects of myeloid-derived suppressor cells in diseases: Role in cancer and infections

Abstract

Myeloid-derived suppressor cells (MDSCs) are heterogeneous cells capable of abrogating T and B cells responses and have been identified in numerous cancers. As with other regulatory cell populations, they aim to maintain balance between host-defence-associated inflammation and ensuing tissue pathology. MDSC accumulation and/or activation involve several growth factors and cytokines including Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Interleukin (IL)-6 and suppression has been linked to receptors such as IL-4Rα. Other immune pathways, such as Toll-like receptors (TLRs) have also been shown to interfere in MDSC activity adding to the complexity in clarifying their pathways. Monocytic- (Mo-MDSCs) and polymorphonuclear- (PMN-MDSCs) cells are two subsets of MDSCs that have been well characterized and have been shown to function through different mechanisms although both appear to require nitric oxide. In human and murine model settings, MDSCs have been shown to have inhibitory effects on T cell responses during bacterial, parasitic and viral pathologies and an increase of MDSC numbers has been associated with pathological conditions. Interestingly, the environment impacts on MDSC activity and regulatory T cells (Tregs), mast cells and a few cells that may help MDSC in order to regulate immune responses. Since the majority of pioneering data on MDSCs has stemmed from research on malignancies, this review will summarize MDSC biology and function in cancer and highlight current knowledge about these cells during infectious pathologies as well.