Yu Han, Cui Guo, Chaoxin Chen, Wenzhuo Yang, Honghui Li, Changjia He, Jialin Deng, Zhijie Chen, Wenfeng Liu, Jiehong Chen, Yingqian Zhong, Caixin Yan, Cuiying Xu, Xuanming Liang, Sheng Zhong, Furong Chen, Depei Li, Cong Li, Wanming Hu, Zhenghe Chen, Yonggao Mou, Zhong Chen, Guangmei Yan, Michael Lim, Wenbo Zhu, Ke Sai
Abstract Glioblastoma multiforme (GBM) is a lethal primary brain cancer with limited treatment options. Systemic and local immunosuppression induced by GBMs contributes to malignancy aggressiveness and resistance to immune checkpoint blockade (ICB) therapy. Herein, we demonstrated that a novel oncolytic virus, M1 (OVM), reversed GBM-driven systemic immunosuppression and promoted T lymphocyte infiltration within the tumor microenvironment (TME). Intravenous administration of OVM suppressed glioma progression in a spleen-dependent manner. Mechanistically, OVM enhanced B-cell–T-cell interactions in the spleen through the formation of immune synapses. A subset of B cells positive for bone marrow stromal cell antigen 2 (Bst2) was enriched in the splenic marginal zone following OVM treatment and exhibited superior capacity for antigen cross-presentation. These splenic Bst2 + B cells activated cognate CD8 + T cells to mediate adaptive antitumor immunity against intracranial gliomas. Moreover, OVM treatment synergized with anti-PD-1 therapy and further extended the survival of glioma-bearing animals. Collectively, our findings highlight the therapeutic potential of intravenous OVM for GBM management and reveal a novel immunomodulatory mechanism underlying oncolytic virotherapy.