溶瘤病毒
溶瘤腺病毒
肿瘤微环境
免疫疗法
癌症研究
免疫系统
癌症免疫疗法
生物
腺病毒科
肿瘤坏死因子α
免疫学
遗传增强
生物化学
基因
作者
Wenmo Liu,Xupu Wang,Xinyao Feng,Jiahao Yu,Xinyao Liu,Xiaoxu Jia,Haihong Zhang,Hui Wu,Chu Wang,Jiaxin Wu,Bin Yu,Xianghui Yu
出处
期刊:Cancer Letters
[Elsevier]
日期:2022-06-01
卷期号:535: 215661-215661
被引量:9
标识
DOI:10.1016/j.canlet.2022.215661
摘要
The immune status of the tumor microenvironment is a key indicator determining the antitumor effect of immunotherapy. Oncolytic viruses directly target tumor cells or indirectly modulate the tumor microenvironment (TME) especially when properly armed. It was previously demonstrated that conditionally replicating adenovirus serotype 5 (CRAd5) encoding tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) had outstanding antitumor effects in different human cancer cells xenograft models; however, its antitumor immune mechanism has not been evaluated in immunocompetent preclinical mouse models. We first explored the antitumor activity of CRAd5-TRAIL in several murine tumor models and found that the expression of TRAIL induced increases or activation in tumor-infiltrating T cells. To further improve the antitumor effects, mouse CD40 ligand (mCD40L) as an immune activator expressed by recombinant Ad5 vector was firstly used in combination with CRAd5-TRAIL for tumor immunotherapy. Both in vitro and in vivo studies demonstrated that mCD40L effectively activated dendritic cells (DCs), B cells, and tumor-infiltrating T cells, and also promoted tumor cell apoptosis by increasing the expression of TRAIL receptors, thereby significantly enhancing the antitumor activity of oncolytic adenoviruses in CT26 and B16 tumor-bearing models. Although affected by the restriction of oncolytic adenovirus replication in mouse cells, the combination treatment failed to completely eliminate tumor cells, our research still provided a promising strategy for oncolytic adenovirus-mediated solid tumor immunotherapy.
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