Tumor vaccination during oncolytic inflammation leads to regulatory T cell-dependent virus/tumor immune interference that facilitates effective cancer immunotherapy

A balance between effector and suppressor mechanisms dictates whether an infection would overcome tolerance mechanism to trigger autoimmunity. In order to shift this balance in favor of antitumoral immunity we performed vaccinations with tumor-antigen loaded dendritic cells before, during or after oncolytic inflammation of a primary tumor. We observed a strongly enhanced antitumoral CD8+ T cell immune response which was accompanied by inhibition of the antiviral humoral immune response and a shift to Th2-immunoglobulin isotype, when DC vaccination was performed at the time of oncolytic inflammation. This interference of the immune responses was dependent on the time of vaccination, local tumor antigen expression and tumorspecific viral replication. Compared to DC tumor vaccination or tumor specific replication alone regression of primary tumors and elimination of virally uninfected lung metastases was significantly improved by the immune interference, leading to improved survival of animals with disseminated tumor growth. While depletion of Tregs significantly enhanced immune responses against intracellular antigens after viral infection or DC vaccination, it abrogated the antitumoral cytotoxicity, inhibited CD8 T cell tumor infiltration and rescued the antiviral humoral immune response in mice with tumor vaccination during oncolytic inflammation. Our results show that DC tumor vaccination at the time of oncolytic tumor inflammation is a promising Treg dependent cancer immunotherapy that facilitates cure of animals with disseminated tumors.

DC vaccination - HCC - Treg - immunotherapy - oncolytic - virotherapy