Oncolytic virotherapy is a promising
biological approach to
cancer treatment that contributes to
tumor eradication via immune- and non-immune-mediated mechanisms. One of the remaining challenges for these
experimental therapies is the necessity to develop a durable adaptive immune response against the
tumor.
Vesicular stomatitis virus (VSV) is a prototypical oncolytic virus (OV) that exemplifies the multiple mechanisms of oncolysis, including direct cell lysis, cellular hypoxia resulting from the shutdown of
tumor vasculature, and inflammatory
cytokine release. Despite these properties, the generation of sustained antitumor immunity is observed only when VSV is engineered to express a
tumor antigen directly. In the present study, we sought to increase the number of
tumor-associated dendritic cells (DC) in vivo and
tumor antigen presentation by combining VSV treatment with recombinant
Fms-like tyrosine kinase 3 ligand (rFlt3L), a
growth factor promoting the differentiation and proliferation of DC. The combination of VSV oncolysis and rFLt3L improved animal survival in two different
tumor models, i.e., VSV-resistant
B16 melanoma and VSV-sensitive E.G7 T
lymphoma; however, increased survival was independent of the adaptive CD8 T cell response.
Tumor-associated DC were actively infected by VSV in vivo, which reduced their viability and prevented their migration to the draining lymph nodes to prime a
tumor-specific CD8 T cell response. These results demonstrate that VSV interferes with
tumor DC functions and blocks
tumor antigen presentation.