溶瘤病毒
胶质瘤
肿瘤微环境
免疫系统
癌症研究
细胞毒性T细胞
生物
溶瘤腺病毒
小胶质细胞
CD8型
病毒
免疫疗法
体内
免疫学
体外
炎症
生物化学
生物技术
作者
Shenglun Li,Yuduo Guo,Weihai Ning,Yujia Chen,Jiacheng Xu,Chao Zhao,Jun Wang,Yanming Qu,Mingshan Zhang,Pengju Wang,Yaohe Wang,Shengdian Wang,Hongwei Zhang
出处
期刊:Life Sciences
[Elsevier]
日期:2024-01-01
卷期号:336: 122254-122254
标识
DOI:10.1016/j.lfs.2023.122254
摘要
Gliomas are the most common central nervous system malignancies, with limited therapeutic options and poor prognosis, which are primarily attributed to the "immune desert" microenvironment. Previously, we constructed a three-gene-deleted oncolytic adenovirus (Ad-TD) loaded with non-secreting interleukin-12 (nsIL-12), which could be amplified in tumor cells and induce immunity to suppress tumors. However, the effects of this oncolytic virus on gliomas and their immune microenvironment remain unclear. There is an urgent need for further research.We constructed a Syrian hamster brain tumor model and demonstrated the efficacy and mechanism of the novel oncolytic virus in treating brain tumors through a series of in vitro and in vivo experiments. We investigated the efficacy and safety (the number of hamsters in each group is either 5 or 10) of the oncolytic virus treatment in Syrian hamsters using a virus-treated group, a control virus-treated group, and a blank control group.In vitro assays showed that Ad-TD-nsIL-12 could specifically proliferate in brain tumor cells which induce tumor cell apoptosis and intracellular expression of interleukin (IL)-12. Moreover, in vivo experiments demonstrated that Ad-TD-nsIL-12 could effectively inhibit the progression of brain tumors and prolong survival. Ad-TD-nsIL-12 significantly enhanced T-cell infiltration in the brain tumor microenvironment.Ad-TD-nsIL-12 can inhibit glioma progression and increase T-cell infiltration in the tumor tissue, particularly infiltration by cytotoxic T cells (CD8+). Ad-TD-nsIL-12 can amplify and produce IL-12, inducing anti-glioma immune responses to inhibit tumor progression.
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