ArticleActa neuropathologica communications2021
TNFα secreted by glioma associated macrophages promotes endothelial activation and resistance against anti-angiogenic therapy.
Article in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 59 citations in OpenAlex.
- Low-dose TNF-α drives malignant progression and lipid metabolism in glioblastoma through the TRAF2-FASN axis.Cell death discovery · 2026Article
- Immunosuppressive mechanisms and therapeutic interventions shaping glioblastoma immunity.Nature cancer · 2026Review
- Association of intratumoral CD68Frontiers in immunology · 2026Article
- Spatiotemporal and metabolic heterogeneity of tumor-associated macrophages in glioblastoma: from single-cell insights to therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- RIPK1 in Diffuse Glioma Pathology: From Prognosis Marker to Potential Therapeutic Target.International journal of molecular sciences · 2025Article
- 5-ALA Assisted Surgery of Human Glioblastoma Samples Reveals an Enrichment of T Cells Expressing PD-1 and CD103 in the Intermediate and Marginal Layers.European journal of immunology · 2025Article
- Insights of immune cell heterogeneity, tumor-initiated subtype transformation, drug resistance, treatment and detecting technologies in glioma microenvironment.Journal of advanced research · 2025Review
- Differential gene expression analysis in French bulldog high grade oligodendroglioma: breed-associated differences in tumor and tumor microenvironment gene expression.Companion animal health and genetics · 2025Article
- Advances in bioengineered CAR T/NK cell therapy for glioblastoma: Overcoming immunosuppression and nanotechnology-based strategies for enhanced CAR T/NK cell therapy.Bioengineering & translational medicine · 2025Review
- Targeting glioma-associated microglia and macrophages: a new frontier in glioblastoma immunotherapy.Frontiers in immunology · 2025Review
- ICAM1-Mediated Endothelial Cells and Macrophage Interactions in Modulating GBM Malignant Transformation.Journal of inflammation research · 2025Article
- New Insights into Monocyte-Derived Macrophages in Glioblastoma.Research (Washington, D.C.) · 2025Review
- Pathophysiological role of histamine signaling and its implications in glioblastoma.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- Review
- Upregulation of HLA-II related to LAG-3Cancer science · 2024Article
- Hypoxia drives shared and distinct transcriptomic changes in two invasive glioma stem cell lines.Scientific reports · 2024Article
- Antibiotics treatment promotes vasculogenesis in the brain of glioma-bearing mice.Cell death & disease · 2024Article
- Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment.Cell & bioscience · 2024Review
- Immunopathology of Extracellular Vesicles in Macrophage and Glioma Cross-Talk.Journal of clinical medicine · 2023Review
- Anti-Vascular Endothelial Growth Factor Therapy Abolishes Glioma-Associated Endothelial Cell-Induced Tumor Invasion.Journal of molecular neuroscience : MN · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
One of the most prominent features of glioblastoma (GBM) is hyper-vascularization. Bone marrow-derived macrophages are actively recruited to the tumor and referred to as glioma-associated macrophages (GAMs) which are thought to provide a critical role in tumor neo-vascularization. However, the mechanisms by which GAMs regulate endothelial cells (ECs) in the process of tumor vascularization and response to anti-angiogenic therapy (AATx) is not well-understood. Here we show that GBM cells secrete IL-8 and CCL2 which stimulate GAMs to produce TNFα. Subsequently, TNFα induces a distinct gene expression signature of activated ECs including VCAM-1, ICAM-1, CXCL5, and CXCL10. Inhibition of TNFα blocks GAM-induced EC activation both in vitro and in vivo and improve survival in mouse glioma models. Importantly we show that high TNFα expression predicts worse response to Bevacizumab in GBM patients. We further demonstrated in mouse model that treatment with B20.4.1.1, the mouse analog of Bevacizumab, increased macrophage recruitment to the tumor area and correlated with upregulated TNFα expression in GAMs and increased EC activation, which may be responsible for the failure of AATx in GBMs. These results suggest TNFα is a novel therapeutic that may reverse resistance to AATx. Future clinical studies should be aimed at inhibiting TNFα as a concurrent therapy in GBMs.
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