The success of
immune checkpoint blockade has unequivocally demonstrated that anti-
tumor immunity plays a pivotal role in
cancer therapy. Because endogenous
tumor-specific T-cell responsiveness is essential for the success of checkpoint blockade, combination
therapy with
cancer vaccination may facilitate
tumor rejection. To select the best
vaccine strategy to combine with checkpoint blockade, we compared dendritic cell-based
vaccines (DC-V) with
peptide vaccines for induction of anti-
tumor immunity that could overcome
tumor-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 and central memory phenotype that were not exhausted.
Vaccine-primed cells were metabolically distinct from naïve cells. DC-V-primed pmel-1 cells contained the population that shifted metabolic 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 optimal anti-
cancer activity in this model.