The success of immune checkpoint blockade has unequivocally demonstratedthat anti-tumor immunity plays a pivotal role in cancer therapy. Becauseendogenous tumor-specific T-cell responsiveness is essentialfor the success of checkpoint blockade, combination therapy withcancer vaccination may facilitate tumor rejection. To select the best vaccine strategy tocombine with checkpoint blockade,we compared dendritic cell-based vaccines(DC-V) with peptide vaccinesfor induction ofanti-tumor immunity that could overcometumor-induced immunosuppression.Using B16 melanoma and B16-specific TCR-transgenic T-cells(pmel-1), we found that DC-V efficiently primed and expanded pmel-1 cells with an active effector andcentral memory phenotype that were not exhausted.Vaccine-primed cells were metabolically distinct from naïve cells. DC-V-primed pmel-1 cellscontained the population that shiftedmetabolic pathways away from glycolysis to mitochondrial oxidative phosphorylation.They displayed better effector function and proliferated more than those induced by peptide vaccination. DC-V inhibited tumor growth in prophylactic and therapeutic settings. Only DC-V but not peptide vaccine showed augmented anti-tumor activity when combined with anti-PD-1 therapy.Thus, DC-V combined with PD-1 checkpoint blockade mediates optimalanti-cancer activity in this model.