栓病毒（reovirus）作为一种天然存在的溶瘤病毒，在肿瘤微环境中通过溶解肿瘤细胞的同时，释放肿瘤抗原或者促凋亡细胞因子来增强抗癌免疫。然而，栓病毒通过对干扰素产生的抑制作用，成功地甄别以逃避抗病毒免疫，进而对抗肿瘤免疫应答进行负面调控。哺乳动物适配蛋白干扰素基因刺激蛋白 （STING）被鉴定为一个重要的调节因子，通过感知源自病原体或肿瘤的细胞内DNA，从而产生I型干扰素。最近的研究报告了STING在对RNA病毒介导的先天性免疫应答中的作用，限制了RNA病毒复制。在本研究中，我们发现在体外条件下，栓病毒与STING激动剂相互作用后，对I型干扰素的反应是互补的。然而，我们发现栓病毒和STING激动剂的联合使用能够通过促进细胞毒性T细胞对肿瘤的移入，增强抗肿瘤免疫力，从而显著减小肿瘤的体积，并提高活存率。我们的数据表明，通过加强肿瘤微环境中的炎症反应，栓病毒和STING激动剂的联合应用可能成为改善栓病毒免疫治疗的一种策略。 © 2023. 作者，独家许可给Springer-Verlag GmbH Germany的一部分，Springer Nature的一部分。

Reovirus, a naturally occurring oncolytic virus, initiates the lysis of tumor cells while simultaneously releasing tumor antigens or proapoptotic cytokines in the tumor microenvironment to augment anticancer immunity. However, reovirus has developed a strategy to evade antiviral immunity via its inhibitory effect on interferon production, which negatively affects the induction of antitumor immune responses. The mammalian adaptor protein Stimulator of Interferon Genes (STING) was identified as a key regulator that orchestrates immune responses by sensing cytosolic DNA derived from pathogens or tumors, resulting in the production of type I interferon. Recent studies reported the role of STING in innate immune responses to RNA viruses leading to the restriction of RNA virus replication. In the current study, we found that reovirus had a reciprocal reaction with a STING agonist regarding type I interferon responses in vitro; however, we found that the combination of reovirus and STING agonist enhanced anti-tumor immunity by enhancing cytotoxic T cell trafficking into tumors, leading to significant tumor regression and survival benefit in a syngeneic colorectal cancer model. Our data indicate the combination of reovirus and a STING agonist to enhance inflammation in the tumor microenvironment might be a strategy to improve oncolytic reovirus immunotherapy.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.