Oncolytic virotherapy with chimeric rVSV-NDV causes tumor-specific immunity in a DC-activation-dependent manner

In recent years, activation of the immune system has been recognized as a key mechanism in supporting the therapeutic outcome of oncolytic virotherapy for cancer. Most studies have focused on T cells in the characterization of immune responses to therapy; however, the role of dendritic cells (DCs) in priming these cytotoxic T cell responses has been far less explored. rVSV-NDV is a chimeric oncolytic virus that causes a highly immunogenic cell death in infected tumor cells. In tumor-bearing mice, this leads to increased levels of circulating and tumor-infiltrating tumor-specific CD8⁺ T cells upon rVSV-NDV treatment. Here, we show that the rVSV-NDV-mediated immunogenic cell death leads to the activation of the dendritic cell subtypes, cDC1 and cDC2, in vitro and in vivo. Using wild-type (WT) and cDC1-deficient (BATF3KO) mice implanted with B16 melanoma lesions, we observed that the increase in circulatory, tumor-specific CD8⁺ T cells and the survival benefit conferred by rVSV-NDV tumor therapy depends on a functional cDC1 population. Finally, we demonstrate that rVSV-NDV therapy can be significantly augmented by the combined treatment with adoptively transferred cDC1 cells that were ex vivo activated and antigen-loaded by co-culture with rVSV-NDV-infected tumor cells.