TGFB1 and neoplasm: Furthermore, the profoundly immunosuppressive tumor microenvironment (TME) contributes to diminished T-cell infiltration and function through multiple mechanisms, including upregulation of inhibitory immune checkpoints (11), HIF-1α-mediated lactate accumulation (12, 13) and elevated TGF-β expression (14), collectively rendering GBM an immunologically "cold" tumor.