Inducing an oxidized redox-balance improves anti-tumor CD8+T cell function

Abstract

SUMMARYCancer immunotherapy using antigen-specific CD8+T cells depends on long-lasting anti-tumor function of thein vitroexpanded T cells. T cell function is intricately linked to the activity of many metabolic pathways directly impacting the ability of CD8+T cells to kill tumor cells. Metabolic conditioningin vitrobetter prepares CD8+T cells forin vivosurvival, tumor infiltration and tumor clearance. The mechanism underlyingin vitrometabolic conditioning-induced augmentedin vivoT cell function remains poorly understood. Here we show that metabolic conditioning of CD8+effector T cells induces an oxidized cellular redox balance at least in part mediated by increased mitochondrial reactive oxygen species (ROS). This redox shift contributes to enhancedin vivopersistence and tumor clearance. In human tumour-infiltrating T cells, altering the redox balanceex-vivoreinvigorated pro-inflammatory cytokine production. Therefore, we believe that redox alterations present a targetable pathway to increase T cell-based anti-tumor immunotherapy efficacy.