These Bregs can be stimulated to secrete TGF-β via multiple pathways, such as the classical signalling involving the TLR, BCR, and CD40 receptors, or growth factor-induced signalling (e.g. phosphatidylinositol-glycan biosynthesis class F protein (PIGF) induced differentiation of TGF-β secreting Bregs in glioma), subjective to the local environment of cells [18]. This evidence concerns the gene TGFB1 and central nervous system cancer.