Bystander cells in the TME also cooperate with myeloma cells in the induction and activation of immune suppressive MDSC via direct mechanisms including: 1) IL-6 release (47, 48); 2) exosome release by BMSC (49); 3) production and release of immune suppressive molecules [i.e. Prostaglandin-Endoperoxide Synthase 2 (PTGS2), TGF-β, Nitric Oxide Synthase 2 (NOS2), IL-10 and IL-6] by MSC and OB (50, 51). The gene discussed is NOS2; the disease is plasma cell myeloma.