Oncolytic viruses have been seriously considered for
glioma therapy over the last 20 years. The oncolytic activity of several oncolytic strains has been demonstrated against human
glioma cell lines and in in vivo xenotransplant models. So far, four of these stains have additionally completed the first phase I/II trials in relapsed
glioma patients. Though safety and feasibility have been demonstrated, therapeutic efficacy in these initial trials, when described, was only minor. The role of the immune system in
oncolytic virotherapy for
glioma remained much less studied until recent years. When investigated, the immune system, adept at controlling
viral infections, is often hypothesized to be a strong hurdle to successful
oncolytic virotherapy. Several preclinical studies have therefore aimed to improve
oncolytic virotherapy efficacy by combining it with immune suppression or evasion strategies. More recently however, a new paradigm has developed in the
oncolytic virotherapy field stating that oncolytic virus-mediated
tumor cell death can be accompanied by elicitation of potent activation of innate and adaptive anti-
tumor immunity that greatly improves the efficacy of certain oncolytic strains. Therefore, it seems the three-way interaction between oncolytic virus,
tumor and immune system is critical to the outcome of antitumor
therapy. In this review we discuss the studies which have investigated how the immune system and oncolytic viruses interact in models of
glioma. The novel insights generated here hold important implications for future research and should be incorporated into the design of novel clinical trials.