Tumours employ a variety of immune-evasion and suppression mechanisms to impair development of functional tumor-specific T cells and subvert T cell-mediated immunity in the tumour microenvironment. Adoptive T cell therapy (ACT) aims to overcome these barriers and overwhelm tumor defenses with a bolus of T cells that were selectively expanded ex vivo. Although this strategy has been effective in liquid tumors and melanomas, many tumors appear to be resistant to ACT. Several factors are thought to play into this resistance, including poor engraftment and persistence of transferred cells, tumour cell heterogeneity and antigen loss, poor immune cell recruitment and infiltration into the tumour, and susceptibility to local immunosuppression in the tumor microenvironment. Oncolytic viruses (OV) have been identified as powerful stimulators of the anti-tumour immune response. As such, OVs are inherently well-positioned to act in synergy with ACT to bolster the anti-tumour T cell response. Further, OV vaccines, wherein tumour-associated antigens are encoded into the viral backbone, have proven to be remarkable in boosting antigen-specific T cell response. Pre-clinical studies have revealed remarkable therapeutic outcomes when OV vaccines are paired with ACT. In this scenario, OV vaccines are thought to function in a “push and pull” manner, where push refers to expanding T cells in the periphery and pull refers to recruiting those cells into the tumour that has been rendered amenable to T cell attack by the actions of the OV. In this review, we discuss barriers that limit eradication of tumors by T cells, highlight attributes of OVs that break down these barriers and present strategies for rational combinations of ACT with OV vaccines.

肿瘤采用多种免疫逃避和抑制机制来损害功能性肿瘤特异性 T 细胞的发育并破坏肿瘤微环境中 T 细胞介导的免疫。过继性 T 细胞疗法 (ACT) 旨在通过体外选择性扩增的大量 T 细胞来克服这些障碍并压倒肿瘤防御. 尽管这种策略在液体肿瘤和黑色素瘤中有效，但许多肿瘤似乎对 ACT 具有抗性。有几个因素被认为会导致这种耐药性，包括转移细胞的植入和持久性差、肿瘤细胞异质性和抗原丢失、免疫细胞募集和浸润到肿瘤中的能力差，以及对肿瘤微环境中局部免疫抑制的易感性。溶瘤病毒 (OV) 已被确定为抗肿瘤免疫反应的强大刺激剂。因此，OVs 天生具有与 ACT 协同作用以加强抗肿瘤 T 细胞反应的良好定位。此外，OV 疫苗，其中肿瘤相关抗原被编码到病毒骨架中，已被证明在增强抗原特异性 T 细胞反应方面非常显着。临床前研究表明，当 OV 疫苗与 ACT 配对时，治疗效果显着。在这种情况下，OV 疫苗被认为以“推拉”方式发挥作用，其中推是指在外周扩大 T 细胞，拉是指将那些细胞募集到肿瘤中，这些细胞已经通过 OV 的作用受到了 T 细胞的攻击。在这篇综述中，我们讨论了限制 T 细胞根除肿瘤的障碍，强调了 OV 打破这些障碍的属性，并提出了 ACT 与 OV 疫苗合理组合的策略。