ArticleCNS neuroscience & therapeutics2023
G9a promotes immune suppression by targeting the Fbxw7/Notch pathway in glioma stem cells.
Article in CNS neuroscience & therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Molecular insights into DNA damage response plasticity in glioma stem cells.Communications biology · 2026Review
- Cancer stem cell heterogeneity‑inspired therapeutics for enhancing tumor treatment outcomes (Review).International journal of oncology · 2026Review
- Transcriptomic profiling of epigenetic regulators and metabolic reprogramming in human cholangiocarcinoma.Frontiers in cell and developmental biology · 2026Article
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Overcoming immunotherapy barriers in pediatric brain tumors: epigenetic strategies.Frontiers in oncology · 2026Review
- [Research Advances on the Immune Evasion Mechanisms of Disseminated Tumor Cells and Their Roles in Cancer Metastasis].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Cancer stem cells: Bridging microenvironmental interactions and clinical therapy.Clinical and translational medicine · 2025Review
- Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights.Biomarker research · 2025Review
- New insights on anti-tumor immunity of CD8Journal of translational medicine · 2025Review
- BRD4 promotes immune escape of glioma cells by upregulating PD-L1 expression.Journal of neuro-oncology · 2025Article
- Cancer stem cells in personalized therapy: mechanisms, microenvironment crosstalk, and therapeutic vulnerabilities.Frontiers in cell and developmental biology · 2025Review
- Epigenetic Modifiers: Exploring the Roles of Histone Methyltransferases and Demethylases in Cancer and Neurodegeneration.Biology · 2024Review
- Role of circular RNAs in preeclampsia (Review).Experimental and therapeutic medicine · 2024Review
- CD147-K148me2-Driven Tumor Cell-Macrophage Crosstalk Provokes NSCLC Immunosuppression via the CCL5/CCR5 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Lysine methylation modifications in tumor immunomodulation and immunotherapy: regulatory mechanisms and perspectives.Biomarker research · 2024Review
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.Journal of hematology & oncology · 2024Review
- Mechanism of Notch Signaling Pathway in Malignant Progression of Glioblastoma and Targeted Therapy.Biomolecules · 2024Review
- Novel insights into Notch signaling in tumor immunity: potential targets for cancer immunotherapy.Frontiers in immunology · 2024Review
- The Role and Mechanism of the Histone Methyltransferase G9a in Tumors: Update.OncoTargets and therapy · 2024Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimImmunotherapy for glioblastoma multiforme (GBM) is limited because of a strongly immunosuppressive tumor microenvironment (TME). Remodeling the immune TME is an effective strategy to eliminate GBM immunotherapy resistance. Glioma stem cells (GSCs) are inherently resistant to chemotherapy and radiotherapy and involved in immune evasion mechanism. This study aimed to investigate the effects of histone methyltransferases 2 (EHMT2 or G9a) on immunosuppressive TME and whether this effect was related to changes on cell stemness.
methodsTumor-infiltrating immune cells were analyzed by flow cytometry and immunohistochemistry in orthotopic implanted glioma mice model. The gene expressions were measured by RT-qPCR, western blot, immunofluorescence, and flow cytometry. Cell viability was detected by CCK-8, and cell apoptosis and cytotoxicity were detected by flow cytometry. The interaction of G9a and F-box and WD repeat domain containing 7 (Fbxw7) promotor was verified by dual-luciferase reporter assay and chromatin immunoprecipitation.
resultsDownregulation of G9a retarded tumor growth and extended survival in an immunocompetent glioma mouse model, promoted the filtration of IFN-γ + CD4+ and CD8+ T lymphocytes, and suppressed the filtration of PD-1+ CD4+ and CD8+ T lymphocytes, myeloid-derived suppressor cells (MDSCs) and M2-like macrophages in TME. G9a inhibition decreased PD-L1 and increased MHC-I expressions by inactivating Notch pathway companying stemness decrease in GSCs. Mechanistically, G9a bound to Fbxw7, a Notch suppressor, to inhibit gene transcription through H3K9me2 of Fbxw7 promotor.
conclusionG9a promotes stemness characteristics through binding Fbxw7 promotor to inhibit Fbxw7 transcription in GSCs, forming an immunosuppressive TME, which provides novel treatment strategies for targeting GSCs in antitumor immunotherapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.