CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8+ T cells via NF-κB signaling

Abstract Background: CD137 is a target for tumor immunotherapy. However, the role of CD137 in gastric cancer (GC), especially in inducing GC cell apoptosis, has not been studied. Methods: Foxp3+ and CD8+ T cells in GCs were investigated using immunohistochemistry (IHC). CD137 expression in GCs was detected using flow cytometry, IHC and immunofluorescence (IF). Peripheral blood mononuclear cells (PBMCs) and CD8+ T cells isolated from peripheral blood were stimulated with a CD137 agonist in vitro. CD8+ T cell proliferation and p65 expression was examined using flow cytometry. P65 nuclear translocation was analyzed using IF. IL-10, TGF-β, IFN-γ, perforin and granzyme B were detected using real-time quantitative PCR (real-time PCR). PBMCs and primary GC cells were cocultured and stimulated with a CD137 agonist in vitro. Apoptosis of primary GC cells was detected using flow cytometry. Results: Our data demonstrated that GC tumors showed characteristics of an immunosuppressive microenvironment. CD137 was predominantly expressed in CD8+ T cells in GCs and had a positive correlation with tumor cell differentiation. The CD137 agonist promoted CD8+ T cell proliferation and increased the secretion of IFN-γ, perforin and granzyme B, which induced primary GC cell apoptosis. Mechanistically, this study found that the CD137 agonist induced NF-κB nuclear translocation in CD8+ T cells. Conclusion: Our results demonstrated that a CD137 agonist induced primary GC cell apoptosis by enhancing CD8+ T cells via activation of NF-κB signaling.