Additionally, the hypoxic environment can affect the proliferation, differentiation, and effector functions of immune cells via the secretion of growth factors and cytokines, such as the pro-angiogenic factor VEGF, which can inhibit DC maturation, regulate TCR signal transduction, and inhibit the expression of perforin (PRF1) and granulysin (GNLY), acting against CD4+ Th1 cells and CTL killing tumor cells (30). Here, PRF1 is linked to neoplasm.