Nagaoka et al. compared the effects of a peptide-pulsed dendritic cell vaccine (DC-V) and a short peptide vaccine (SP-V) in a B16 melanoma model and found that the combination of DC-V/anti-PD-1 slowed tumor growth, while SP-V/anti-PD-1 did not. DC-V-primed T cells in the spleen had a higher central/effector memory phenotype ratio, fewer exhaustion markers, and metabolism that was shifted from glycolysis to oxidative phosphorylation compared to SP-V-primed T cells.

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 naive 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.

Author Info: (1) Department of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-Ku, Tokyo, Japan. Medinet Co. Ltd., Kohoku-Ku, Yokohama, Japan. (2) Department of Immunotherapeutics, The University of

Author Info: (1) Department of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-Ku, Tokyo, Japan. Medinet Co. Ltd., Kohoku-Ku, Yokohama, Japan. (2) Department of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-Ku, Tokyo, Japan. Medinet Co. Ltd., Kohoku-Ku, Yokohama, Japan. (3) Department of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-Ku, Tokyo, Japan. Medinet Co. Ltd., Kohoku-Ku, Yokohama, Japan. (4) Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan. (5) Department of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-Ku, Tokyo, Japan. (6) Department of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-Ku, Tokyo, Japan.

Less