Figure 3.

The role of myeloid-derived suppressor cells (MDSCs) in breast cancer: Common immunogenic pathways of MDSCs in breast cancer progression are the induction of immunosuppression by iNOS, NOS, ROS, Arg1, IL-10, TGF-β, and PD-L1, thus facilitating immune evasion of tumor cells. Non-immunogenic mechanisms include the enhancement of cancer stemness by the nitric oxide (NO)-induced Notch/ signal transducer and activator of transcription 3 (STAT3) pathway, matrix metallopeptidase (MMP) 9, and chitinase 3-like 1 and the promotion of tumor invasiveness by the IL-6/IL6Rα/STAT pathway, phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway, and MMP upregulation. During metastasis, MDSCs differentiate into osteoclasts, which increases osteolytic bone metastasis and promotes MMP, TGF-β1, VEGF, IL-10, and versican secretion, and into metastasis-associated macrophages.