ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
The Impact of Macrophage- and Microglia-Secreted TNFα on Oncolytic HSV-1 Therapy in the Glioblastoma Tumor Microenvironment.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 95 citations in OpenAlex.
- Oncolytic Herpes Simplex Virus for Glioblastoma: Molecular Engineering, Tumor Microenvironment Barriers, and Clinical Translation.Current issues in molecular biology · 2026Review
- Low-dose TNF-α drives malignant progression and lipid metabolism in glioblastoma through the TRAF2-FASN axis.Cell death discovery · 2026Article
- Oncolytic human herpesvirus for cancer therapy.Molecular biology reports · 2026Review
- Advancements on the synergistic application of oncolytic viruses and molecularly targeted therapies for the treatment of solid tumors (Review).International journal of oncology · 2026Review
- Resistance to oncolytic virotherapy: Multidimensional mechanisms and therapeutic breakthroughs (Review).International journal of molecular medicine · 2025Review
- Alphavirus replicons encoding IFN-γ enhance cancer virotherapy by overcoming macrophage-mediated suppression.iScience · 2025Article
- Review
- A zinc transporter drives glioblastoma progression via extracellular vesicles-reprogrammed microglial plasticity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Multi-omics analysis reveals key immunogenic signatures induced by oncolytic Zika virus infection of paediatric brain tumour cells.Scientific reports · 2025Article
- Understanding the interplay between oHSV and the host immune system: Implications for therapeutic oncolytic virus development.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Targeting glioma-associated microglia and macrophages: a new frontier in glioblastoma immunotherapy.Frontiers in immunology · 2025Review
- Unmasking the potential: mechanisms of neuroinflammatory modulation by oncolytic viruses in glioblastoma.Exploration of targeted anti-tumor therapy · 2025Review
- Article
- Oncolytic virus and tumor-associated macrophage interactions in cancer immunotherapy.Clinical and experimental medicine · 2024Review
- OV Modulators of the Paediatric Brain TIME: Current Status, Combination Strategies, Limitations and Future Directions.International journal of molecular sciences · 2024Review
- Upregulation of HLA-II related to LAG-3Cancer science · 2024Article
- Molecular Circuits of Immune Sensing and Response to Oncolytic Virotherapy.International journal of molecular sciences · 2024Review
- Comparison of differences in immune cells and immune microenvironment among different kinds of oncolytic virus treatments.Frontiers in immunology · 2024Review
- Improving the therapeutic efficacy of oncolytic viruses for cancer: targeting macrophages.Journal of translational medicine · 2023Review
- Clinical advances in oncolytic virus therapy for malignant glioma: a systematic review.Discover oncology · 2023Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
purposeOncolytic herpes simplex viruses (oHSV) represent a promising therapy for glioblastoma (GBM), but their clinical success has been limited. Early innate immune responses to viral infection reduce oHSV replication, tumor destruction, and efficacy. Here, we characterized the antiviral effects of macrophages and microglia on viral therapy for GBM. EXPERIMENTAL
designQuantitative flow cytometry of mice with intracranial gliomas (±oHSV) was used to examine macrophage/microglia infiltration and activation. In vitro coculture assays of infected glioma cells with microglia/macrophages were used to test their impact on oHSV replication. Macrophages from TNFα-knockout mice and blocking antibodies were used to evaluate the biologic effects of TNFα on virus replication. TNFα blocking antibodies were used to evaluate the impact of TNFα on oHSV therapy in vivo.
resultsFlow-cytometry analysis revealed a 7.9-fold increase in macrophage infiltration after virus treatment. Tumor-infiltrating macrophages/microglia were polarized toward a M1, proinflammatory phenotype, and they expressed high levels of CD86, MHCII, and Ly6C. Macrophages/microglia produced significant amounts of TNFα in response to infected glioma cells in vitro and in vivo. Using TNFα-blocking antibodies and macrophages derived from TNFα-knockout mice, we discovered TNFα-induced apoptosis in infected tumor cells and inhibited virus replication. Finally, we demonstrated the transient blockade of TNFα from the tumor microenvironment with TNFα-blocking antibodies significantly enhanced virus replication and survival in GBM intracranial tumors.
conclusionsThe results of these studies suggest that FDA approved TNFα inhibitors may significantly improve the efficacy of oncolytic virus therapy.
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