Abstract
Selective destruction of neoplastic tissues by oncolytic viruses (OVs) leads to antigen-agnostic boosting of neoantigen-specific cytotoxic T lymphocyte (CTL) responses, making OVs ideal companions for checkpoint blockade therapy. Here we discuss the mechanisms whereby OVs modulate both adjuvanticity and antigenicity of tumor cells. Suppression of antitumor immunity after OV therapy has not been observed, possibly because viral antigen expression diminishes as the antiviral response matures, thereby progressively honing the CTL response to tumor neoantigens. By combining direct in situ tumor destruction with the ability to boost antitumor immunity, OVs also have the potential to be powerful standalone cancer therapies.