Viral vaccines improve PD-1 therapy against cancer

Abstract

Abstract Programmed cell death-1 (PD-1) therapy is effective against various types of cancer. However, only 30% of cancers respond to PD-1 therapy, highlighting the need to further improve its efficacy. In this study, we interrogated whether one could exploit the immunostimulatory properties of viral vaccines to enhance PD-1 therapy in a B16 melanoma model that is poorly responsive to PD-1 therapy. Immunization of tumor-bearing mice with clinically approved viral vaccines, such as the smallpox virus vaccine and the yellow fever virus vaccine (YFV-17D), resulted in an unprecedented improvement of PD-1 therapy. This synergistic effect on PD-1 therapy was more potent upon a secondary immunization, suggesting a positive effect of recruiting pre-existent immune memory to the tumor microenvironment. Interestingly, co-administration of viral vaccines together with PD-1 therapy did not increase tumor-specific CD8 T cell responses relative to PD-1 therapy alone. Mechanistically, the adjuvant effect of viral vaccines on PD-1 therapy seems to be dependent on innate immune responses. These findings may be important for improving the efficacy of checkpoint-based immunotherapies by exploiting the immunogenicity of viral vaccines. Altogether, our data suggest that viral vaccines could be repurposed as immunotherapy adjuvants, and that the beneficial effects of viral vaccines on PD-1 therapy can be further improved by repetitive boosting of bystander immunity. R21 AI132848-01A1 (NIAID); IRG-15-173-21 (ACS), and the Lurie Cancer Center.