PMC

Schematic description of the models of MDSC accumulation that require either one or two signals. HPC – hematopoietic progenitor cells. IMC – immature myeloid cells that have phenotype similar to MDSC but lacking immune suppressive activity

Bacterial and viral products, as well as cytokines released by activated T cells or myeloid cells induce activation of Stat1, Stat6 and TLR signaling. Stat1 and Stat6 act directly and TLR signaling via MyD88 and NF-κB to up-regulate proteins directly involved in the immune suppressive activity of MDSC.

Various cytokines produced by tumors or bone marrow stroma in response to chronic infections or inflammation activate several signal transduction pathways that result in activation of Stat3, Stat5. Stat3 regulates transcription of subunits of Nox2 that results in increased production of ROS, as well as up-regulation of a number of anti-apoptotic proteins and possibly CEBPβ that, in turn, up-regulate c-myc. All together these proteins contribute to proliferation and survival of immature myeloid cells and prevent their differentiation to mature cells. This manifests in expansion of cells with the phenotype of MDSC.