Year: 2026
Type: article
Abstract: Immunotherapy with oncolytic Herpes simplex virus type 1 (oHSV-1) shows promise for glioblastoma; however, clinical benefit remains uncommon due to tumour- and host-mediated immunosuppression, which limits immune targeting of residual glioblastoma stem-like cells (GSCs). To address this barrier, extracellular vesicles (EVs) harvested from oHSV-1-infected GSCs (EVOV) were evaluated for their immunomodulatory capacity by priming peripheral blood mononuclear cells (PBMCs) ex vivo and in vivo. In GSC-PBMC organoids analysed by single-cell RNA sequencing, IFN-response and antigen-presentation programs were induced in both immune and tumour compartments, despite the GSC state. EVOV organoid transcriptome associated with patient tumour antigen-processing programs linked to improved clinical outcome, and EVOV immunopeptidomics identified candidate biomarker peptides that were also detected in patient immunopeptidomes from the clinical-trial cohort. In PBMC-engrafted NOD scid gamma mice bearing intracranial GSC xenografts, EVOV delivery increased circulating interferon (IFN) levels and enhanced systemic activation of T-cell subsets, while spatial transcriptomics revealed recruitment of peripheral immune cells to the tumour, accompanied by reprogramming of GSC states. Blocking vesicle-associated major histocompatibility complex I (MHC-I) attenuated EVOV-driven PBMC cytotoxicity against GSCs, supporting an MHC-I peptide-dependent mechanism of immune priming and a vaccine- or adjuvant-like, non-infectious, vesicle-based immunotherapeutic strategy.
DOI: 10.1002/jev2.70389
Authors: Klaudia Kiel, Arpita Balakrishnan, Aleksandra Cabaj, Luiza Stanaszek, Maciej Przybylski, Dawid Stępnik, Marta Małuszek, Christopher Jannotta, Chiara Zoe Linke, Joanna Suszyńska‐Zajczyk, Monika Knaur, Agnieszka Szczypiorowska, Szymon Hryhorowicz, Bianka Świderska, Katarzyna Piwocka, Alexander Lee Ling, E. Antonio Chiocca, Agnieszka Bronisz, Jakub Godlewski
Institutions: Mossakowski Medical Research Institute, Polish Academy of Sciences, Instytut Biologii Doświadczalnej im. Marcelego Nenckiego, Polish Academy of Sciences, Medical University of Warsaw, Brigham and Women's Hospital, Harvard University, Institute of Human Genetics, Poznań University of Life Sciences, Institute of Biochemistry and Biophysics, Polish Academy of Sciences
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,410
Funders: Narodowym Centrum Nauki, Instytut Biologii Doswiadczalnej im. M. Nenckiego PAN, Narodowa Agencja Wymiany Akademickiej, Agencja Badań Medycznych, National Institutes of Health, European Regional Development Fund, National Cancer Institute, National Institute of Neurological Disorders and Stroke
OpenAlex ID: W7223179551