文章：

双向切割：对溶瘤病毒治疗的先天免疫反应

Cutting both ways: the innate immune response to oncolytic virotherapy

原文发布日期：2021-08-27 

英文摘要：

Oncolytic viruses (OVs), above and beyond infecting and lysing malignant cells, interact with the immune system in complex ways that have important therapeutic significance. While investigation into these interactions is still in its early stages, important insights have been made over the past two decades that will help improve the clinical efficacy of OV-based management strategies in cancer care moving forward. The inherent immunosuppression that defines the tumor microenvironment can be modified by OV infection, and the subsequent recruitment and activation of innate immune cells, in particular, is central to this. Indeed, neutrophils, macrophages, natural killer cells, and dendritic cells, as well as other populations such as myeloid-derived suppressor cells, are key to the immune escape that allows tumors to survive, but their natural response to infection can be exploited by virotherapy. While stimulation of innate immune cells by OVs can initiate antitumor responses, related antiviral activity can limit virus spread and direct cytopathogenic effects. In this review, we highlight how each innate immune cell population influences this balance of antitumor and antiviral forces during virotherapy, some of the important molecular pathways that have been identified, and specific therapeutic targets that have emerged through this work. We discuss the importance of OV-based combination therapies in optimizing antiviral and antitumor innate immune responses stimulated by virotherapy toward tumor eradication, and how these processes vary depending on the tumor and OV in question. Rather than concentrating on a particular OV species in the review, we present the range of effects that have been documented across OV types to emphasize the context-specific nature of these interactions and how this is important in the design of future OV-based treatment approaches. 

摘要翻译：

溶瘤病毒（OVs）除了感染和裂解恶性细胞外，更以复杂的方式与免疫系统相互作用，这种相互作用具有重要的治疗意义。尽管对这些相互作用的研究仍处于早期阶段，但过去二十年来已取得重要发现，这些发现将有助于提高基于OV的癌症治疗策略的临床疗效。肿瘤微环境固有的免疫抑制特性可通过OV感染发生改变，其中随后天然免疫细胞（特别是中性粒细胞、巨噬细胞、自然杀伤细胞和树突状细胞）的招募与激活至关重要。事实上，这些细胞群体以及髓源性抑制细胞等其他群体，既是肿瘤赖以存活的免疫逃逸关键，但其对感染的自然反应又可被病毒疗法利用。虽然OV对天然免疫细胞的刺激可启动抗肿瘤反应，但相关的抗病毒活动可能限制病毒扩散和直接细胞病理效应。本综述重点阐述了在病毒治疗过程中，各类天然免疫细胞群体如何影响抗肿瘤与抗病毒力量的平衡，已发现的重要分子通路，以及通过这项研究涌现的具体治疗靶点。我们讨论了基于OV的联合疗法在优化病毒治疗激发的抗病毒/抗肿瘤天然免疫反应以实现肿瘤清除方面的重要性，并分析了这些过程如何因肿瘤类型和所用OV的不同而产生差异。本文未聚焦特定OV种类，而是通过展示不同OV类型中已记录的作用谱系，强调这些相互作用的背景特异性特征，及其对未来设计基于OV的治疗方案的重要意义。

原文链接：

Cutting both ways: the innate immune response to oncolytic virotherapy