Antitumor Benefits of Antiviral Immunity: An Underappreciated Aspect of Oncolytic Virotherapies

Oncolytic viruses (OVs) represent a new class of cancer immunotherapeutics. Administration of OVs to cancer-bearing hosts induces two distinct immunities: antiviral and antitumor. While antitumor immunity is beneficial, antiviral immune responses are often considered detrimental for the efficacy of OV-based therapy. The existing dogma postulates that anti-OV immune responses restrict viral replication and spread, and thus reduce direct OV-mediated killing of cancer cells. Accordingly, a myriad of therapeutic strategies aimed at mitigating anti-OV immune responses is presently being tested. Here, we advocate that OV-induced antiviral immune responses hold intrinsic anticancer benefits and are essential for establishing clinically desired antitumor immunity. Thus, to achieve the optimal efficacy of OV-based cancer immunotherapies, strategic management of anti-OV immune responses is of critical importance. OVs can preferentially infect and kill malignant cancer cells, without imparting similar lytic effects on normal cells. In addition to their direct oncolytic activity, OVs can awaken the otherwise suppressed immune system of cancer-bearing hosts and consequently promote beneficial antitumor immunity. This is an indispensable part of OV-based cancer therapies. The antiviral immune response induced by OVs restricts viral replication and spread, and is often considered detrimental for the efficacy of therapy as it can prematurely curtail direct oncolytic activities. However, antiviral immune responses induced by OVs can reverse tumor-mediated suppression of innate and adaptive immunity, and are thus essential for the development of clinically desired OV-induced antitumor responses.