Since Tregs constitute a major subset of CD4+ T cells, elevation in Treg/CD4+ T-cell ratio (with pronounced expression of CTLA-4) in TME leads to the inhibition of tumor-reactive T cells, either by direct cell contact or through TGF-β and IL-10, correlating with the disease progression in glioma patients (169, 170). Here, CD4 is linked to central nervous system cancer.