Using oncolytic viruses to ignite the tumour immune microenvironment in bladder cancer

Despite the success of immune checkpoint inhibition (ICI) in other tumour types, the majority of ICI-treated patients with bladder cancer fail to respond. This lack of efficacy might be attributable to a lack of pre-existing immune reactive cells within the tumour immune microenvironment, which limits the efficacy of ICI. In this Review, Li and colleagues discuss how oncolytic virus therapy acts as a strategy to attract lymphocytes before implementation of ICI and consider the data supporting the use of combination approaches using oncolytic virotherapy with ICI in bladder cancer. The advent of immune checkpoint inhibition (ICI) has transformed the treatment paradigm for bladder cancer. However, despite the success of ICI in other tumour types, the majority of ICI-treated patients with bladder cancer failed to respond. The lack of efficacy in some patients could be attributed to a paucity of pre-existing immune reactive cells within the tumour immune microenvironment, which limits the beneficial effects of ICI. In this setting, strategies to attract lymphocytes before implementation of ICI could be helpful. Oncolytic virotherapy is thought to induce the release of damage-associated molecular patterns, eliciting a pro-inflammatory cytokine cascade and stimulating the activation of the innate immune system. Concurrently, oncolytic virotherapy-induced oncolysis leads to further release of neoantigens and subsequent epitope spreading, culminating in a robust, tumour-specific adaptive immune response. Combination therapy using oncolytic virotherapy with ICI has proven successful in a number of preclinical studies and is beginning to enter clinical trials for the treatment of both non-muscle-invasive and muscle-invasive bladder cancer. In this context, understanding of the mechanisms underpinning oncolytic virotherapy and its potential synergism with ICI will enable clinicians to effectively deploy oncolytic virotherapy, either as monotherapy or as combination therapy in the different clinical stages of bladder cancer.