Distinguishing the pros and cons of metabolic reprogramming in oncolytic virus immunotherapy

Oncolytic viruses (OVs) represent a class of cancer immunotherapies that rely on hijacking the host cell factory for replicative oncolysis and eliciting immune responses for tumor clearance. An increasing evidence suggests that the metabolic state of tumor cells and immune cells is a putative determinant of the efficacy of cancer immunotherapy. However, how therapeutic intervention with OVs affects metabolic fluxes within the tumor microenvironment (TME) remains poorly understood. Herein, we review the complexities of metabolic reprogramming involving the effects of viruses and their consequences on tumor cells and immune cells. We highlight the inherent drawback of oncolytic virotherapy, namely that treatment with OVs inevitably further exacerbates the depletion of nutrients and the accumulation of metabolic wastes in the TME, leading to a metabolic barrier to antitumor immune responses. We also describe targeted metabolic strategies that can be used to unlock the therapeutic potential of OVs.