Initially, direct oncolysis was thought to be the sole mechanism through which oncolytic viruses (OVs) exert their anti-tumor effect, and the immune system was perceived as the major obstacle in oncolytic virotherapy. Over the last decade, there has been a lot of debate on whether the immune system is a friend or foe of OVs. However, we are now at a stage where the initial thinking has been reversed as a result of compelling evidence that the immune system plays a critical role in the success of oncolytic virotherapy. In this review we discuss the importance of the involvement of innate and adaptive immunity for therapeutic efficacy of OVs, and the rational combination of OVs with other immunotherapies for further enhancement of overall therapeutic outcome.
