Oncolytic Zika virus promotes intratumoral T cell infiltration and improves immunotherapy efficacy in glioblastoma
Lishu Chen, Chao Zhou, Qi Chen, Jingzhe Shang, Zhaodan Liu, Yan Guo, Chunfeng Li, Hong-Jiang Wang, Qing Ye, Xiaofeng Li, Shulong Zu, Fangye Li, Qing Xia, Tao Zhou, Ailing Li, Chenhui Wang, Yun Chen, Aiping Wu, Cheng‐Feng Qin, Jianghong Man
Abstract
T cell intratumoral infiltration and activation in GBM mouse models. ZIKV treatment of mice bearing GBM tumors inhibits tumor growth and prolongs survival. These therapeutic effects of ZIKV on GBM tumors are negated in mice depleted of T cells. Moreover, ZIKV dramatically promotes activation of the type I interferon signaling pathway in GBM cells. ZIKV treatment potently sensitizes GBM to PD-L1 blockade and provides significant and durable survival benefits. Our findings reveal that ZIKV overcomes the resistance of GBM to immune checkpoint blockade, which may lead to therapeutic applications of ZIKV in individuals with GBM receiving immunotherapy.