Figure 3.

Mechanisms of action underlying the efficacy of oncolytic viruses (OVs). Mechanistic pathways are categorized as immune-mediated and non-immune pathways. Non-immune pathways are utilized by OVs to avoid apoptotic (non-immunogenic) death to allow sufficient viral infectivity and spread, while at the same time resulting in cell lysis. Connecting non-immune and immune pathways is antigen release as a result of viral infection-induced cell lysis. The mechanism underlying immune-mediated pathways includes delivery or utilization of immune mediators that allow for improved tumor antigen presentation and subsequent tumor-targeted immune responses. Radiation therapy and chemotherapy (leading to cell lysis and antigen release) and immunotherapy (leading to blockade of antitumor response suppression and exhaustion) are being combined with OVs to simultaneously target multiple mechanistic pathways for improved antitumor therapeutic responses. Mechanisms of action are listed in red text. Single examples of viruses utilizing each of the described mechanisms are listed in black text next to their respective mechanism. Mediators responsible for each mechanism are listed in blue text next to their respective mechanism. Therapies used in combination regimens with OVs are listed in green text.