ArticleFrontiers in immunology2020
Constitutive Expression of the Immunosuppressive Tryptophan Dioxygenase TDO2 in Glioblastoma Is Driven by the Transcription Factor C/EBPβ.
Article in Frontiers in immunology, 2020. 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, 35 citations in OpenAlex.
- Intravenous administration of LPS activates the kynurenine pathway in healthy male human subjects: a prospective placebo-controlled cross-over trial.Journal of neuroinflammation · 2021Trial
- Metabolic Reprogramming and Neurotransmitter Signaling Co-Option in the Glioma Immune Microenvironment: Dual-Axis Regulation of Immunosuppression.Biomolecules · 2026Review
- Tryptophan metabolism in tumor immune escape: mechanisms, cellular crosstalk, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Unraveling the complexities of diet induced obesity and glucolipid dysfunction in metabolic syndrome.Diabetology & metabolic syndrome · 2025Review
- Glioblastoma at the crossroads: current understanding and future therapeutic horizons.Signal transduction and targeted therapy · 2025Review
- Therapeutic targeting of the tryptophan-kynurenine-aryl hydrocarbon receptor pathway with apigenin in MED12-mutant leiomyoma cells.Cancer gene therapy · 2025Article
- Mechanics of serotonin-producing human entero-endocrine cells.Mechanobiology in medicine · 2024Article
- Implications of Kynurenine Pathway Metabolism for the Immune System, Hypothalamic-Pituitary-Adrenal Axis, and Neurotransmission in Alcohol Use Disorder.International journal of molecular sciences · 2024Review
- Targeting amino acid-metabolizing enzymes for cancer immunotherapy.Frontiers in immunology · 2024Review
- Tryptophan Metabolism and Gut Microbiota: A Novel Regulatory Axis Integrating the Microbiome, Immunity, and Cancer.Metabolites · 2023Review
- Participation of protein metabolism in cancer progression and its potential targeting for the management of cancer.Amino acids · 2023Review
- Metabolic partitioning in the brain and its hijacking by glioblastoma.Genes & development · 2023Review
- Review
- The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer.Frontiers in oncology · 2023Review
- Bioinformatic Analysis of Kynurenine Pathway Enzymes and Their Relationship with Glioma Hallmarks.Metabolites · 2022Article
- The Kynurenine Pathway and Cancer: Why Keep It Simple When You Can Make It Complicated.Cancers · 2022Review
- Environmental Phenol and Paraben Exposure Risks and Their Potential Influence on the Gene Expression Involved in the Prognosis of Prostate Cancer.International journal of molecular sciences · 2022Article
- The Epigenetics of Psychosis: A Structured Review with Representative Loci.Biomedicines · 2022Review
- Identification and Characterization of a Novel Dual Inhibitor of Indoleamine 2,3-dioxygenase 1 and Tryptophan 2,3-dioxygenase.International journal of tryptophan research : IJTR · 2022Article
- Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Catabolism of the essential amino acid tryptophan is a key metabolic pathway contributing to the immunosuppressive tumor microenvironment and therefore a viable drug target for cancer immunotherapy. In addition to the rate-limiting enzyme indoleamine-2,3-dioxygenase-1 (IDO1), tryptophan catabolism via tryptophan-2,3-dioxygenase (TDO2) is a feature of many tumors, particularly malignant gliomas. The pathways regulating TDO2 in tumors are poorly understood; using unbiased promoter and gene expression analyses, we identify a distinct CCAAT/enhancer-binding protein β (C/EBPβ) binding site in the promoter of TDO2 essential for driving constitutive TDO2 expression in glioblastoma cells. Using The Cancer Genome Atlas (TCGA) data, we find that C/EBPβ expression is correlated with TDO2, and both are enriched in malignant glioma of the mesenchymal subtype and associated with poor patient outcome. We determine that TDO2 expression is sustained mainly by the LAP isoform of CEBPB and interleukin-1β, which activates TDO2 via C/EBPβ in a mitogen-activated protein kinase (MAPK) kinase-dependent fashion. In summary, we provide evidence for a novel regulatory and therapeutically targetable pathway of immunosuppressive tryptophan degradation in a subtype of glioblastoma with a particularly poor prognosis.
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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 OpenQuestion graph.