ArticleScientific reports2019
Exhaustion of CD4+ T-cells mediated by the Kynurenine Pathway in Melanoma.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Exploring the Etiological Links behind Neurodegenerative Diseases: Inflammatory Cytokines and Bioactive Kynurenines.International journal of molecular sciences · 2020Pooled it
- Tryptophan degradation by intestinal Bacteroides induces anti-tumor immunity and limits melanoma growth.Cell reports. Medicine · 2026Article
- Immunometabolic Stress and Immune Suppression in Clear-Cell Renal Cell Carcinoma: Perspectives in Therapeutic Strategy.International journal of molecular sciences · 2026Review
- Cell Signaling by Tryptophan Catabolism.Biochemistry · 2026Review
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- Efficacy of FOXP3+Treg cells combined with platelet in predicting recurrence of cervical cancer: a retrospective study.BMC women's health · 2026Article
- Single-Cell Transcriptome Atlas Reveals the Underlying Mechanism of Kynurenic Acid in the Regulation of Tumor Immune Microenvironment in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The aryl hydrocarbon receptor and kynurenine pathway: connecting inflammatory bowel disease and depression via the microbiota gut brain axis.Frontiers in neuroscience · 2026Review
- Metabolic Cross Talk in the Tumor Microenvironment.Cancer treatment and research · 2026Review
- Metabolomics of Prostate Cancer and Clinical Profiles Following Radiotherapy: Need for a Precision Phylometabolomics Approach.Diagnostics (Basel, Switzerland) · 2025Article
- Cancer cells accelerate exhaustion of persistently activated mouse CD4Oncoimmunology · 2025Article
- Utilization of AhR and GPR35 Receptor Ligands as Superfoods in Cancer Prevention for Individuals with IBD.International journal of molecular sciences · 2025Review
- NAMPT and NNMT released via extracellular vesicles and as soluble mediators are distinguished traits of BRAF inhibitor resistance of melanoma cells impacting on the tumor microenvironment.Cell communication and signaling : CCS · 2025Article
- The tumor microenvironment of non-small cell lung cancer impairs immune cell function in people with HIV.The Journal of clinical investigation · 2025Article
- Integrated single cell and bulk RNA sequencing analyses reveal the impact of tryptophan metabolism on prognosis and immunotherapy in colon cancer.Scientific reports · 2025Article
- Targeting the Kynurenine Pathway: A Novel Approach in Tumor Therapy.Expert reviews in molecular medicine · 2025Review
- TDO2 inhibition counters Benzo[a]pyrene-induced immune evasion and suppresses tumorigenesis in lung adenocarcinoma.Cancer & metabolism · 2024Article
- Double-Edge Effects of Leucine on Cancer Cells.Biomolecules · 2024Review
- Applying metabolic control strategies to engineered T cell cancer therapies.Metabolic engineering · 2024Review
- Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kynurenine pathway (KP) activation by the enzymatic activity of indoleamine 2,3-dioxygenase1 (IDO1) and kynurenine (KYN) production represents an attractive target for reducing tumour progression and improving anti-tumour immunity in multiple cancers. However, immunomodulatory properties of other KP metabolites such as 3-hydroxy kynurenine (3-HK) and kynurenic acid (KYNA) are poorly understood. The association of the kynurenine metabolic pathway with T-cell status in the tumour microenvironment were characterized, using gene expression data of 368 cutaneous skin melanoma (SKCM) patients from the TCGA cohort. Based on the identified correlations, we characterized the production of KYN, 3-HK, and KYNA in vitro using melanoma-derived cell lines and primary CD4+ CD25- T-cells. Activation of the CD4+ T-cells produced IFNγ, which yielded increased levels of KYN and KYNA. Concurrently, kynurenine 3-monooxygenase (KMO) expression and proliferation of CD4+ T-cells were reduced, whereas exhaustion markers such as PD-L1, AHR, FOXP3, and CTLA4 were increased. Additionally, an analysis of the correlation network reconstructed using TCGA-SKCM emphasized KMO and KYNU with high variability among BRAF wild-type compared with V600E, which underscored their role in distinct CD4+ T-cell behavior in tumour immunity. Our results suggest that, in addition to IDO1, there is an alternative immune regulatory mechanism associated with the lower KMO expression and the higher KYNA production, which contributes to dysfunctional effector CD4+ T-cell response.
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Registered trials
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.