Characterization of virus-mediated immunogenic cancer cell death and the consequences for oncolytic virus-based immunotherapy of cancer
Characterization of virus-mediated immunogenic cancer cell death and the consequences for oncolytic virus-based immunotherapy of cancer
复制标题
DOI：
10.1038/s41419-020-2236-3
复制
发表时间：
2020-01-22
影响因子：
9
通讯作者：
Essand, Magnus
中科院分区：
文献类型：
--
作者：
Ma, Jing;Ramachandran, Mohanraj;Essand, Magnus
溶瘤病毒有可能诱导免疫原性细胞死亡(ICD)，从而可能激发强大而持久的抗癌免疫。本研究旨在研究野生型腺病毒(Ad)、塞姆利基森林病毒(SFV)和痘苗病毒(VV)诱导ICD的能力。我们通过研究病毒杀死的肿瘤细胞的细胞死亡和免疫激活特性来做到这一点。肿瘤细胞的腺病毒感染主要激活自噬，但也激活坏死性和嗜酸性细胞死亡事件。另一方面，SFV感染主要激活免疫原性细胞凋亡，而VV感染则激活坏死性下垂。所有病毒都介导肿瘤细胞的裂解，导致危险相关分子模式的释放，触发树突状细胞(DC)的吞噬和成熟。然而，只有感染SFV的肿瘤细胞才能激发树突状细胞显著释放Th1类细胞因子并诱导抗原特异性T细胞活化。我们的结果阐明了Ad、SFV和VV感染后激活的细胞死亡过程以及它们诱导T细胞介导的抗肿瘤免疫反应的可能性。这一知识为选择和设计治疗上成功的基于病毒的免疫疗法提供了重要的见解。
Oncolytic viruses have the potential to induce immunogenic cell death (ICD) that may provoke potent and long-lasting anti-cancer immunity. Here we aimed to characterize the ICD-inducing ability of wild-type Adenovirus (Ad), Semliki Forest virus (SFV) and Vaccinia virus (VV). We did so by investigating the cell death and immune-activating properties of virus-killed tumor cells. Ad-infection of tumor cells primarily activates autophagy, but also activate events of necroptotic and pyroptotic cell death. SFV infection on the other hand primarily activates immunogenic apoptosis while VV activates necroptosis. All viruses mediated lysis of tumor cells leading to the release of danger-associated molecular patterns, triggering of phagocytosis and maturation of dendritic cells (DCs). However, only SFV-infected tumor cells triggered significant T helper type 1 (Th1)-cytokine release by DCs and induced antigen-specific T-cell activation. Our results elucidate cell death processes activated upon Ad, SFV, and VV infection and their potential to induce T cell-mediated anti-tumor immune responses. This knowledge provides important insight for the choice and design of therapeutically successful virus-based immunotherapies.