Graduate Institute of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan.
Mol Ther. 2012 Feb;20(2):298-305. doi: 10.1038/mt.2011.245. Epub 2011 Nov 8.
Sindbis virus (SBV) has been shown to possess oncolytic potential in many human xenograft tumor models in immunocompromised mice. However, the mechanism underlying the tumor selectivity of SBV remains undetermined. In this study, we provide evidence that the tumor tropism of SBV infection is not determined by the levels of SBV receptor but by the status of the type I interferon (IFN) response in the tumors. Our results demonstrate that cells with defects in the IFN response (in either IFN-β production or IFN signaling) were highly susceptible to SBV infection in vitro. The results of oncolysis experiments conducted in immunocompetent animals further confirmed that the success of SBV-mediated oncolysis is greatly dependent on the presence of defects in IFN signaling in tumors. In all cases, viral titers rapidly declined in tumors due to host immune responses in immunocompetent animals. Interestingly, however, tumor-specific immune responses were concomitantly elicited, which might contribute to the sustained antitumor effect observed after the clearance of SBV. These findings indicate that SBV-mediated virotherapy is a promising therapeutic strategy for cancers defective in the IFN response and underscore the importance of bystander antitumor immunity in the efficacy of this virotherapy.
辛德毕斯病毒（SBV）已被证明在免疫功能低下的小鼠的许多人异种移植肿瘤模型中具有溶瘤潜力。然而，SBV 肿瘤选择性的机制仍未确定。在这项研究中，我们提供了证据表明，SBV 感染的肿瘤趋向性不是由 SBV 受体的水平决定的，而是由肿瘤中 I 型干扰素（IFN）反应的状态决定的。我们的结果表明，在 IFN 反应中存在缺陷的细胞（IFN-β产生或 IFN 信号转导）在体外对 SBV 感染高度敏感。在免疫功能正常的动物中进行的溶瘤实验的结果进一步证实，SBV 介导的溶瘤的成功在很大程度上取决于肿瘤中 IFN 信号转导的缺陷。在所有情况下，由于免疫功能正常的动物中的宿主免疫反应，病毒滴度在肿瘤中迅速下降。然而，有趣的是，同时引发了肿瘤特异性免疫反应，这可能有助于在清除 SBV 后观察到持续的抗肿瘤效应。这些发现表明，SBV 介导的病毒疗法是一种有前途的治疗策略，适用于 IFN 反应缺陷的癌症，并强调了旁观者抗肿瘤免疫在这种病毒疗法中的重要性。
