CTLA4 and cancer: Hypoxia, a condition intrinsic to tumor rapid growth and vascularization, promotes VEGF secretion by tumor cells and M2 macrophages and TGFβ production by M2 macrophages, which collectively upregulate PD-L1 expression on cancer cells and CTLA4 ligand CD86 on DCs, and inhibit tumor cell recognition through costimulatory receptor NKG2D on NK and T cells36.