Abstract
Background:Dendritic cell (DC)‐based vaccines are recognized as a promising immunotherapeutic strategy against cancer, and various combination approaches have been developed to enhance DC function by modulating immune responses and tumor microenvironment.Aims:In this study, we investigated the efficacy of DC vaccination in combination with pomalidomide and programmed death ligand‐1 (PD‐L1) blockade in a murine model of multiple myeloma (MM).Methods:MOPC‐315 cell lines were injected subcutaneously to establish MM bearing mice. Four test groups were used to mimic clinical protocol: (1) PBS control, (2) DCs + pomalidomide/dexamethasone, (3) Pomalidomide/dexamethasone + PD‐L1 blockade, and (4) DCs + pomalidomide/dexamethasone + PD‐L1 blockade.Results:The combination of DCs + pomalidomide with dexamethasone + PD‐L1 blockade inhibited more strongly tumor growth and prolonged survival of treated mice compared to the other groups. This effect was associated with a significant reduction in immune suppressor cells, such as myeloid‐derived suppressor cells, regulatory T cells, and M2 macrophages, and level of immunosuppressive factors, such as vascular endothelial growth factor, transforming growth factor‐β, and interleukin‐10, and with the significant induction of immune effector cells, such as CD4+ and CD8+ T cells, memory T cells, natural killer (NK) cells, and M1 macrophages, in the spleen and tumor microenvironment. Functional activities of cytotoxic T lymphocytes and NK cells in spleen were also enhanced by the combination of DCs + pomalidomide with dexamethasone + PD‐L1 blockade.Summary/Conclusion:The collective findings in the murine MM model suggest that DC vaccination combined with pomalidomide and PD‐L1 blockade synergistically enhance antitumor immunity through two‐way mechanism, which inhibits immunosuppressive cells while activating effector cells with superior polarization of the Th1/Th2 balance in favor of the tumor immune response.
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