Abstract Text: γδ-T cell-based cellular tumor immunotherapy has achieved success in some cancer patients, but the rapid exhaustion of proliferation and effector responses in γδ-T cells caused by repetitive phosphoantigens stimulation limit their clinical application. In this study, using a novel formula by treating the peripheral γδ-T cells with vitamin B5 (VB5), we found that VB5 significantly increased the proliferation of Vγ9Vδ2-T cells with enhanced effector functions against different cancer cells. Exogenous administration of VB5 reprogrammed and increased the oxidative phosphorylation (OXPHOS), which further promoted the proliferation of phosphoantigen-expanded Vγ9Vδ2-T cells and increased the productions of lytic granules like granzyme A/B and perforin, and effector cytokine IFN-γ for enhancing their anti-tumor activities against tumor cells. In murine tumor model, treatment of Vγ9Vδ2-T cells with VB5 controlled tumor growth and prolonged mice survival. Our study offers a novel approach by treated Vγ9Vδ2-T cells with VB5, which reprogram their bioenergetic profile toward OXPHOS pathway and then enhance their proliferation and the efficacy of γδ-T cell-based tumor therapy.
