PGE₂ regulates immunosuppressive cells and their functions by (a) inducing MDSC differentiation and production of PD-L1 and arginase I; (b) shifting macrophages from M1 to M2, inducing PD-L1 expression, and reducing macrophage phagocytosis; and (c) inducing differentiation and migration of Tregs. PGE₂ regulates DCs and their functions through inhibition of differentiation and maturation; induction of T cell tolerance and IL-23 expression; and induction of dedifferentiation of DCs to MDSCs. PGE₂ regulates Th cells and their functions by inducing differentiation and recruitment of Th17, and shifting Th cells from Th1 to Th2. PGE₂ regulates CD8⁺ T cells and their functions by induction of proliferation and tumor antigen–specific tolerance and reduction of CD8⁺ T cell cytotoxicity. PGE₂ regulates NKs and their functions via suppression of cell activation and proliferation and induction of cell apoptosis.