ArticleJCI insight2024
Hypoxia-induced complement component 3 promotes aggressive tumor growth in the glioblastoma microenvironment.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Complement receptor C3aR marks heterogeneous tumor-associated macrophage states associated with improved survival in IDH-wildtype glioblastoma.Brain pathology (Zurich, Switzerland) · 2026Article
- Complement-Targeted Therapies in Glioblastoma: A Systematic Review.Biomedicines · 2026Review
- Integrated Bulk and Single-Cell Transcriptomics Reveals the C3-C3AR1 Axis as a Candidate Mediator of Coagulome-Immune Crosstalk in Osteosarcoma.Biomedicines · 2026Article
- Complement system-related gene signatures implicated in the recurrence of glioma.Translational cancer research · 2026Article
- Exploring shared biomarkers and their mechanisms in thyroid cancer and systemic lupus erythematosus via bioinformatics analysis.Discover oncology · 2026Article
- Coordinated Multicellular Immune Programs and Drug Targets Revealed by Single-Cell Analysis in Driver-Mutated NSCLC.International journal of molecular sciences · 2026Article
- Heterogeneity, Measurement, and Clinical Implications of Oxygenation, Cell Signaling, and Redox Biology in Glioblastoma and Adult Diffuse Gliomas, with Context from Other Brain Tumors.Antioxidants (Basel, Switzerland) · 2026Review
- Review
- Astrocytes in neuroinflammation and brain cancer.Molecular biomedicine · 2026Review
- The complement system contributes to the immunosuppressive microenvironment of uveal melanoma.Journal of translational medicine · 2026Article
- Prognostic value of a combined model integrating clinical and PET radiomics parameters in metastatic melanoma: A dual-center retrospective study.Annals of nuclear medicine · 2026Article
- Decoding myeloid heterogeneity in glioblastoma: spatial insights from transcriptomics.Journal of translational medicine · 2026Review
- Oxygen-dependent modulation of the human complement system during acute normobaric hypoxia: a translational plasma proteomics study.Clinical and experimental medicine · 2026Article
- The Extracellular Matrix, the Silent 'Architect' of Glioma.Biomedicines · 2026Review
- Targeting the C3 signaling axis of the complement system: immune microenvironment regulation and emerging therapeutic strategies for glioblastoma.Frontiers in immunology · 2026Review
- The link between macrophage polarization and response to radiotherapy in cancers: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- The Role of the C3a-C3aR Pathway in Diseases: Latest Research Advances.Mediators of inflammation · 2026Review
- Spatial profiling of longitudinal glioblastoma reveals consistent changes in cellular architecture, post-treatment.Neuro-oncology · 2025Article
- A Prognostic Neuromodulation-Related Gene Signature Identifies Immunomodulation and Tumour-Associated Hallmarks in Glioblastoma.Biomedicines · 2025Article
- Spatial transcriptomics of glioblastoma defines biologically and clinically significant reprogramming patterns across unique spatial microenvironments.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma (GBM) is the most aggressive form of glioma with a high rate of relapse despite intensive treatment. Tumor recurrence is tightly linked to radio-resistance, which in turn is associated with hypoxia. Here, we discovered a strong link between hypoxia and local complement signaling using publicly available bulk, single-cell, and spatially resolved transcriptomic data from patients with GBM. Complement component 3 (C3) and the receptor C3AR1 were both associated with aggressive disease and shorter survival in human glioma. In a genetically engineered mouse model of GBM, we found C3 specifically in hypoxic tumor areas. In vitro, we found an oxygen level-dependent increase in C3 and C3AR1 expression in response to hypoxia in several GBM and stromal cell types. C3a induced M2 polarization of cultured microglia and macrophages in a C3aR-dependent fashion. Targeting C3aR using the antagonist SB290157 prolonged survival of glioma-bearing mice both alone and in combination with radiotherapy while reducing the number of M2-polarized macrophages. Our findings establish a strong link between hypoxia and complement pathways in GBM and support a role of hypoxia-induced C3a/C3aR signaling as a contributor to glioma aggressiveness by regulating macrophage polarization.
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