VEGFA and central nervous system cancer: Also, low oxygen tension leads vascular ECs within the hypoxic niche to produce several factors, such as VEGF-A, which confer a more aggressive behavior to glioma CSCs and polarize immune cells into an immunosuppressive phenotype, as it is demonstrated by tumor-associated macrophage (TAM) M2 polarization, increased regulatory T cells, and higher rates of PD-1+ CD8+ T cells, leading to treatment resistance to traditional and modern approaches such as immunotherapy (Escribese et al., 2012; Tamura et al., 2018, 2019a,b) (Figure 2).