Cytomegalovirus Infection Is Associated with Accelerated Murine Glioblastoma Progression and Alterations in the Tumor Microenvironment
7 affiliations
- 1Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Mass General Brigham Neuroscience Institute, Boston, MA 02115, USA
- 2Harvard Medical School, Boston, MA 02115, USA
- 3Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
- 4Department of Pathology and Laboratory Medicine, Legorreta Cancer Center, Brown University, Providence, RI 02903, USA
- 5Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
- 6Center for Tumors of the Nervous System, Mass General Brigham Cancer Institute, Boston, MA 02114, USA
- 7Department of Surgery, Mass General Brigham, Boston, MA 02115, USA
Abstract
Glioblastoma (GBM) is a highly aggressive brain tumor with no effective treatments. It is characterized by rapid progression and marked heterogeneity, which contributes to therapeutic resistance. Human cytomegalovirus (hCMV), a highly prevalent β-herpesvirus, has been associated with GBM in numerous studies, and both antiviral drugs and hCMV-targeted immunotherapies have shown evidence of therapeutic activity in clinical trials. However, the mechanisms underlying this association remain poorly understood. To address this, we previously developed a murine model of GBM with murine CMV (mCMV) infection, which revealed accelerated tumor progression in infected mice. Here, we investigated whether tumor heterogeneity influences the effects of mCMV infection on intracranial tumor growth across four murine GBM models (GL261, CT-2A, M005 and Mut3). Tumor progression was monitored longitudinally by MRI and evaluated by survival analysis, histopathology and characterization of the tumor microenvironment. Systemic mCMV infection was associated with accelerated GBM progression across all models, characterized by increased tumor growth and significantly reduced survival. Enhanced tumor progression was accompanied by increased vascularization, elevated myeloid cell activation and intratumoral viral activity in a subset of tumors. Mass cytometry (CyTOF) revealed remodeling of the tumor immune landscape, including a marked increase in intratumoral virus-specific CD8+ T cells, highlighting a potential avenue for therapeutic targeting. Together, these findings indicate that CMV is associated with accelerated GBM progression across genetically distinct murine models, accompanied by remodeling of the tumor microenvironment, including increased vascularization and altered immune infiltration.
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BibTeX
@article{zdioruk2026cytomegalovirus,
title = {{Cytomegalovirus Infection Is Associated with Accelerated Murine Glioblastoma Progression and Alterations in the Tumor Microenvironment}},
author = {Mykola Zdioruk and Eleni Panagioti and Noe B. Mercado and Vincent van Unen and Ennio Antonio Chiocca and Michal O. Nowicki and James A. Lederer and Sean E. Lawler and Charles H. Cook},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15211957},
url = {https://www.mdpi.com/2073-4409/15/21/1957},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cytomegalovirus Infection Is Associated with Accelerated Murine Glioblastoma Progression and Alterations in the Tumor Microenvironment
AU - Mykola Zdioruk
AU - Eleni Panagioti
AU - Noe B. Mercado
AU - Vincent van Unen
AU - Ennio Antonio Chiocca
AU - Michal O. Nowicki
AU - James A. Lederer
AU - Sean E. Lawler
AU - Charles H. Cook
PY - 2026
DA - 2026/10/28
JO - Cells
DO - 10.3390/cells15211957
UR - https://www.mdpi.com/2073-4409/15/21/1957
AB - Glioblastoma (GBM) is a highly aggressive brain tumor with no effective treatments. It is characterized by rapid progression and marked heterogeneity, which contributes to therapeutic resistance. Human cytomegalovirus (hCMV), a highly prevalent β-herpesvirus, has been associated with GBM in numerous studies, and both antiviral drugs and hCMV-targeted immunotherapies have shown evidence of therapeutic activity in clinical trials. However, the mechanisms underlying this association remain poorly understood. To address this, we previously developed a murine model of GBM with murine CMV (mCMV) infection, which revealed accelerated tumor progression in infected mice. Here, we investigated whether tumor heterogeneity influences the effects of mCMV infection on intracranial tumor growth across four murine GBM models (GL261, CT-2A, M005 and Mut3). Tumor progression was monitored longitudinally by MRI and evaluated by survival analysis, histopathology and characterization of the tumor microenvironment. Systemic mCMV infection was associated with accelerated GBM progression across all models, characterized by increased tumor growth and significantly reduced survival. Enhanced tumor progression was accompanied by increased vascularization, elevated myeloid cell activation and intratumoral viral activity in a subset of tumors. Mass cytometry (CyTOF) revealed remodeling of the tumor immune landscape, including a marked increase in intratumoral virus-specific CD8+ T cells, highlighting a potential avenue for therapeutic targeting. Together, these findings indicate that CMV is associated with accelerated GBM progression across genetically distinct murine models, accompanied by remodeling of the tumor microenvironment, including increased vascularization and altered immune infiltration.
SN - 2073-4409
ER -