Oncolytic Virus-Engineered Extracellular Vesicles Rewire Glioblastoma Immunity.
11 affiliations
- 1Tumor Microenvironment Laboratory, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
- 2Translational Medicine Doctoral School, Center of Postgraduate Medical Education, Warsaw, Poland.
- 3Laboratory of Sequencing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
- 4NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
- 5Department of Medical Microbiology, Medical University of Warsaw, Warsaw, Poland.
- 6The Laboratory of Cytometry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
- 7Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
- 8Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland.
- 9Department of Biochemistry and Biotechnology, Poznań University of Life Sciences, Poznań, Poland.
- 10Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
- 11Department of NeuroOncology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
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.
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BibTeX
@article{kiel2026oncolytic,
title = {{Oncolytic Virus-Engineered Extracellular Vesicles Rewire Glioblastoma Immunity.}},
author = {Klaudia Kiel and Arpita Balakrishnan and Aleksandra Cabaj and Luiza Stanaszek and Maciej Przybylski and Dawid Stępnik and Marta Małuszek and Christopher Jannotta and Chiara Zoe Linke and Joanna Suszyńska-Zajczyk and Monika Knaur and Agnieszka Szczypiorowska and Szymon Hryhorowicz and Bianka Świderska and Katarzyna Piwocka and Alexander Lee Ling and E Antonio Chiocca and Agnieszka Bronisz and Jakub Godlewski},
journal = {Journal of extracellular vesicles},
year = {2026},
month = oct,
doi = {10.1002/jev2.70389},
url = {https://europepmc.org/article/MED/42908192},
note = {CC BY},
}
RIS
TY - JOUR
TI - Oncolytic Virus-Engineered Extracellular Vesicles Rewire Glioblastoma Immunity.
AU - Klaudia Kiel
AU - Arpita Balakrishnan
AU - Aleksandra Cabaj
AU - Luiza Stanaszek
AU - Maciej Przybylski
AU - Dawid Stępnik
AU - Marta Małuszek
AU - Christopher Jannotta
AU - Chiara Zoe Linke
AU - Joanna Suszyńska-Zajczyk
AU - Monika Knaur
AU - Agnieszka Szczypiorowska
AU - Szymon Hryhorowicz
AU - Bianka Świderska
AU - Katarzyna Piwocka
AU - Alexander Lee Ling
AU - E Antonio Chiocca
AU - Agnieszka Bronisz
AU - Jakub Godlewski
PY - 2026
DA - 2026/10/01
JO - Journal of extracellular vesicles
DO - 10.1002/jev2.70389
UR - https://europepmc.org/article/MED/42908192
AB - 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.
SN - 2001-3078
ER -