biostudies-literatureZhang XNatural Science Foundation of Zhejiang ProvinceNational Natural Science Foundation of ChinaNational Key Research and Development ProgramResearch and Development Program of Zhejiang Provincee003982https://www.ebi.ac.uk/biostudies/studies/S-EPMC8906048biostudies-literatureUnknown10(3)<h4>Backgrounds</h4>In advanced pancreatic ductal adenocarcinoma (PDAC), immune therapy, including immune checkpoint inhibitors, has limited efficacy, encouraging the study of combination therapy.<h4>Methods</h4>Tumor necrosis factor receptor 2 (TNFR2) was analyzed via immunohistochemistry, immunofluorescence, western blotting, and ELISAs. The in vitro mechanism that TNFR2 regulates programmed cell death 1 ligand 1 (PD-L1) was investigated using immunofluorescence, immunohistochemistry, flow cytometry, western blotting, and chromatin immunoprecipitation (ChIP). In vivo efficacy and mechanistic studies, using C57BL/6 mice and nude mice with KPC cell-derived subcutaneous and orthotopic tumors, employed antibodies against TNFR2 and PD-L1. Survival curves were constructed for the orthotopic moJournal for immunotherapy of cancerCombination cancer immunotherapy targeting TNFR2 and PD-1/PD-L1 signaling reduces immunosuppressive effects in the microenvironment of pancreatic tumors.PMC8906048818300892019C0301981871925U20A203782019YFC1316000820718672020C03117LQ22H160044Yang HLiang TJiang HYing HHe LBai XXu JLi MZhang XChen WLao MGuo CDuan YSun KfalseCombination cancer immunotherapy targeting TNFR2 and PD-1/PD-L1 signaling reduces immunosuppressive effects in the microenvironment of pancreatic tumors.<h4>Backgrounds</h4>In advanced pancreatic ductal adenocarcinoma (PDAC), immune therapy, including immune checkpoint inhibitors, has limited efficacy, encouraging the study of combination therapy.<h4>Methods</h4>Tumor necrosis factor receptor 2 (TNFR2) was analyzed via immunohistochemistry, immunofluorescence, western blotting, and ELISAs. The in vitro mechanism that TNFR2 regulates programmed cell death 1 ligand 1 (PD-L1) was investigated using immunofluorescence, immunohistochemistry, flow cytometry, western blotting, and chromatin immunoprecipitation (ChIP). In vivo efficacy and mechanistic studies, using C57BL/6 mice and nude mice with KPC cell-derived subcutaneous and orthotopic tumors, employed antibodies against TNFR2 and PD-L1. Survival curves were constructed for the orthotopic mo2022-01-01T00:00:00Z2022 Mar2026-06-02T09:37:43.451Z2026-05-26T03:06:28.864ZS-EPMC89060483526043410.1136/jitc-2021-003982