The transformation of healthy cells to malignant often drives them to become inherently susceptible to viral infection as a trade-off to achieve uninhibited growth and immune escape. Enter oncolytic viruses (OVs), an exciting class of viruses that specifically infect cancer cells, leaving healthy tissue unharmed. Unfortunately, there is more to this story. Tumours are much more than a group of cancer cells, the surrounding tumour microenvironment (TME) comprises a collection of cells which influence and nourish the development and spread of the tumour. While initially quite promising, OV therapy has been met with a myriad of barriers due to the unwelcoming nature of the TME. Riddled with immunosuppressive factors and physical barriers, many tumours have proven impenetrable by OVs. Herein, we review the diverse array of approaches being used to target each component of the TME from enhancing entry into specific tumour types, breaking through the dense tumour stroma, eliminating cancer stem cells, and activating the immune system. We highlight the value of combination approaches which have led to complete successes in several in vivo models, some of which have entered clinical development.

健康细胞向恶性细胞的转化通常会促使它们变得天生易受病毒感染，作为实现不受抑制的生长和免疫逃逸的权衡。进入溶瘤病毒 (OV)，这是一类令人兴奋的病毒，可以特异性感染癌细胞，而不会伤害健康组织。不幸的是，这个故事还有更多。肿瘤不仅仅是一组癌细胞，周围的肿瘤微环境 (TME) 包括影响和滋养肿瘤发展和扩散的细胞集合。虽然最初很有希望，但由于 TME 不受欢迎的性质，OV 疗法遇到了无数障碍。充满免疫抑制因素和物理障碍，许多肿瘤已被证明无法被 OVs 穿透。在此处，我们回顾了用于靶向 TME 各个组成部分的多种方法，包括增强进入特定肿瘤类型、突破致密的肿瘤基质、消除癌症干细胞和激活免疫系统。我们强调组合方法的价值，这些方法已在多个领域取得了圆满成功。体内模型，其中一些已进入临床开发。