Deciphering permissivity of human tumor ecosystems to oncolytic viruses

Effective cancer therapy involves initiation of a tumor-specific immune response. Consequently, the interest in oncolytic viruses (OV) capable of triggering immunogenic cell death has sparked in recent years. However, the common use of pre-clinical models that fail to mirror patient tumor ecosystems (TES) hinders clinical translation. Here, we provide a condensed view on the intricate interplay between several aspects of TES and OV action and discuss these considerations in the view of recently developed pre-clinical human model systems. Given the urgent demand for innovative cancer treatments, the purpose of this review is to highlight the so-far overlooked complex impact of the tumor microenvironment (TME) on OV permissivity, with the intent to provide a foundation for future, more effective pre-clinical studies.