CD274 and neoplasm: In tumor cells, PD-L1 is upregulated not only through tumor-promoting pathways, such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), but also by factors from the tumor immune microenvironment (TIM) and by a hypoxic microenvironment, which stimulates HIF-1 expression [39] (Figure 1B).