Securinine bolsters anti-tumor immunity by promoting CD8⁺ T cell activation

• Securinine promotes T cell-mediated cytotoxicity • Securinine boosts T cell receptor activation • Securinine enhances the effector function of CD8+ T cells • Combination of securinine and anti-PD-1 suppress tumor growth in mice Securinine (SEC) is a natural alkaloid isolated from Flueggea suffruticosa , which can suppress tumor growth of some types. T cells play a critical role in anti-tumor function. However, whether SEC mediates T cell-mediated anti-tumor effects remains unknown. Here, we found that SEC treatment suppressed tumor growth and improved survival in tumor-bearing mice in vivo . SEC promotes the percentage of IFN-γ + CD8 + T cell and TNF-α + CD8 + T cell in tumor microenvironments. SEC promoted T cell-mediated cytotoxicity in B16F10-OVA and OT-I co-culture systems. The anti-tumor function of SEC was abrogated after depleting CD8 + T cells in tumor-bearing mice. Mechanistically, SEC promoted T cell receptor (TCR) activation, increased IL-2 and IFN-γ production, and enhanced mitochondrial metabolism in CD8 + T cells. Additionally, SEC combination with anti-PD-1 suppressed tumor growth and improved survival in tumor-bearing mice. Thus, SEC enhances anti-tumor immunity by promoting CD8 + T cell activation, suggesting its potential role in tumor immunotherapy.