AUTHOR=Qi Zhongbing , Zhao Jing , Li Yuhua , Zhang Bin , Hu Shichuan , Chen Yanwei , Ma Jinhu , Shu Yongheng , Wang Yunmeng , Cheng Ping TITLE=Live-attenuated Japanese encephalitis virus inhibits glioblastoma growth and elicits potent antitumor immunity JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.982180 DOI=10.3389/fimmu.2023.982180 ISSN=1664-3224 ABSTRACT=

Glioblastomas (GBMs) are highly aggressive brain tumors that have developed resistance to currently available conventional therapies, including surgery, radiation, and systemic chemotherapy. In this study, we investigated the safety of a live attenuated Japanese encephalitis vaccine strain (JEV-LAV) virus as an oncolytic virus for intracerebral injection in mice. We infected different GBM cell lines with JEV-LAV to investigate whether it had growth inhibitory effects on GBM cell lines in vitro. We used two models for evaluating the effect of JEV-LAV on GBM growth in mice. We investigated the antitumor immune mechanism of JEV-LAV through flow cytometry and immunohistochemistry. We explored the possibility of combining JEV-LAV with PD-L1 blocking therapy. This work suggested that JEV-LAV had oncolytic activity against GBM tumor cells in vitro and inhibited their growth in vivo. Mechanistically, JEV-LAV increased CD8+ T cell infiltration into tumor tissues and remodeled the immunosuppressive GBM microenvironment that is non-conducive to immunotherapy. Consequently, the results of combining JEV-LAV with immune checkpoint inhibitors indicated that JEV-LAV therapy improved the response of aPD-L1 blockade therapy against GBM. The safety of intracerebrally injected JEV-LAV in animals further supported the clinical use of JEV-LAV for GBM treatment.