CD274 and neoplasm: The reduced tumor perfusion results in a hypoxic and acidic milieu, which promotes reprogramming of macrophages into an immunosuppressive phenotype, impairs tumor killing functions of immune cells, and up-regulates the expression of inhibitory immune checkpoint molecules, such as programmed death-ligand 1 (PD-L1), by immune, stromal, and tumor cells (Fig. 3) (46–51).