Unlike memory T cell differentiation in acute immune responses, exhausted T cells in GBM fail to sustain long-term antitumor immunity due to persistent antigen exposure, metabolic stress, and an immunosuppressive TME.254 The TME of GBM suppresses T cell activation through inhibitory cytokines such as TGF-β, IL-10, and IL-35,255,256 along with an abundance of regulatory immune cells, including Tregs. This evidence concerns the gene TGFB1 and glioblastoma.