Thus, the mechanisms by which TNFR2 blockade enhances the efficacy of immunotherapy in pancreatic cancer are as follows: (1) direct inhibition of cancer cell proliferation via inhibiting NFκB p65/survial pathways (c-Myc, cyclin D and CDK2); and (2) relief of tumor immunosuppression by downregulating the expression of PD-L1 via the NF-κB p65/PD-L1 pathway and reducing the number of Tregs and TAMs to reinvigorate exhausted T cells. This evidence concerns the gene TNFRSF1B and familial pancreatic carcinoma.