Our study also highlights a mechanism of action in the TNFR family for agonist therapy and suggests that the reciprocal interaction of TGF-β-induced CD73 with 4-1BB costimulatory signals in T cells may be a promising target for both positively and negatively manipulating the anti-tumor immune response (summarized in Supplementary Fig. 12). This evidence concerns the gene TGFB1 and neoplasm.