ArticleNeuro-oncology2022
ATRX loss promotes immunosuppressive mechanisms in IDH1 mutant glioma.
Article in Neuro-oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Pooled it
- The microenvironment of glioblastoma: in pursuit of universal multimodal immunotherapy.Acta neurologica Belgica · 2026Review
- Spatiotemporal dynamics of radioresistance: decoding macrophage-driven radioprotective niches through temporal-spatial reprogramming.Molecular cancer · 2026Review
- The chromatin guardian ATRX is a strong prognostic biomarker in melanoma.Scientific reports · 2025Article
- Immunotherapy and targeted therapy for high grade gliomas: current and future directions.Journal of neuro-oncology · 2025Review
- The Prognostic Value of a Nomogram Model Based on Tumor Immune Markers and Clinical Factors for Adult Primary Glioma.Cancers · 2025Article
- Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.Acta neuropathologica communications · 2025Review
- OncoImmune machine-learning model predicts immune response and prognosis in leiomyosarcoma.Biomolecules & biomedicine · 2025Article
- Integrating Multiplex Immunohistochemistry and Machine Learning for Glioma Subtyping and Prognosis Prediction.MedComm · 2025Article
- Deep visual proteomics reveals DNA replication stress as a hallmark of signet ring cell carcinoma.NPJ precision oncology · 2025Article
- Unraveling Glioblastoma: TME Implication and Gene Therapy Advances.Current gene therapy · 2025Review
- IDH1 and ATRX mutations synergistically modulate cell proliferation and ferroptosis in glioblastoma cells.American journal of cancer research · 2025Article
- Mapping the functional network of human cancer through machine learning and pan-cancer proteogenomics.Nature cancer · 2025Article
- Article
- Article
- Knockdown of ATRX enhances radiosensitivity in glioblastoma.Chinese neurosurgical journal · 2024Article
- Epigenetic regulation of tumor-immune symbiosis in glioma.Trends in molecular medicine · 2024Review
- Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas.Current issues in molecular biology · 2024Review
- Interplay between ATRX and IDH1 mutations governs innate immune responses in diffuse gliomas.Nature communications · 2024Article
- Mutant ATRX: pathogenesis of ATRX syndrome and cancer.Frontiers in molecular biosciences · 2024Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundATRX inactivation occurs with IDH1R132H and p53 mutations in over 80% of Grades II/III astrocytomas. It is believed that ATRX loss contributes to oncogenesis by dysregulating epigenetic and telomere mechanisms but effects on anti-glioma immunity have not been explored. This paper examines how ATRX loss contributes to the malignant and immunosuppressive phenotypes of IDH1R132H/p53mut glioma cells and xenografts.
methodsIsogenic astrocytoma cells (+/-IDH1R132H/+/-ATRXloss) were established in p53mut astrocytoma cell lines using lentivirus encoding doxycycline-inducible IDH1R132H, ATRX shRNA, or Lenti-CRISPR/Cas9 ATRX. Effects of IDH1R132H+/-ATRXloss on cell migration, growth, DNA repair, and tumorigenicity were evaluated by clonal growth, transwell and scratch assays, MTT, immunofluorence and immunoblotting assays, and xenograft growth. Effects on the expression and function of modulators of the immune microenvironment were quantified by qRT-PCR, immunoblot, T-cell function, macrophage polarization, and flow cytometry assays. Pharmacologic inhibitors were used to examine epigenetic drivers of the immunosuppressive transcriptome of IDH1R132H/p53mut/ATRXloss cells.
resultsAdding ATRX loss to the IDH1R132H/p53mut background promoted astrocytoma cell aggressiveness, induced expression of BET proteins BRD3/4 and an immune-suppressive transcriptome consisting of up-regulated immune checkpoints (e.g., PD-L1, PD-L2) and altered cytokine/chemokine profiles (e.g., IL33, CXCL8, CSF2, IL6, CXCL9). ATRX loss enhanced the capacity of IDH1R132H/p53mut cells to induce T-cell apoptosis, tumorigenic/anti-inflammatory macrophage polarization and Treg infiltration. The transcriptional and biological immune-suppressive responses to ATRX loss were enhanced by temozolomide and radiation and abrogated by pharmacologic BET inhibition.
conclusionsATRX loss activates a BRD-dependent immune-suppressive transcriptome and immune escape mechanism in IDH1R132H/p53mut astrocytoma cells.
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