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  3. Oncolytic virus M1 reinvigorates CD8+ T-cell immunity against glioblastoma through B-cell-dependent antigen cross-presentation in the spleen

Oncolytic virus M1 reinvigorates CD8+ T-cell immunity against glioblastoma through B-cell-dependent antigen cross-presentation in the spleen

  • Cell Mol Immunol. 2026 Apr;23(4):349-366. doi: 10.1038/s41423-026-01396-w.
Yu Han # 1,  Cui Guo # 1,  Chaoxin Chen # 2,  Wenzhuo Yang # 1,  Honghui Li 2,  Changjia He 1,  Jialin Deng 1,  Zhijie Chen 3,  Wenfeng Liu 2,  Jiehong Chen 2,  Yingqian Zhong 2,  Caixin Yan 2,  Cuiying Xu 2,  Xuanming Liang 2,  Sheng Zhong 1,  Furong Chen 1,  Depei Li 1,  Cong Li 4,  Wanming Hu 5,  Zhenghe Chen 1,  Yonggao Mou 1,  Zhongping Chen 1,  Guangmei Yan 2,  Michael Lim 6,  Wenbo Zhu 7,  Ke Sai 8
Affiliations

Affiliations

  • 1 Department of Neurosurgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • 2 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • 3 Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University Lingnan Hospital, Guangzhou, China.
  • 4 The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
  • 5 Department of Pathology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • 6 Department of Neurosurgery, Stanford School of Medicine, Palo Alto, CA, USA.
  • 7 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. [email protected].
  • 8 Department of Neurosurgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China. [email protected].
  • # Contributed equally.
PMID: 41781696 DOI: 10.1038/s41423-026-01396-w
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.

Keywords

Antigen cross-presentation; B cell; Glioma; Oncolytic virus.

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