ArticleJournal for immunotherapy of cancer2023
Tryptophan depletion sensitizes the AHR pathway by increasing AHR expression and GCN2/LAT1-mediated kynurenine uptake, and potentiates induction of regulatory T lymphocytes.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Global research status and development trends of chronic obstructive pulmonary disease and gut microbiota: a comprehensive analysis based on bibliometrics and knowledge visualization.Frontiers in microbiology · 2026Pooled it
- Balancing essential amino acids in low-protein diets: Impacts on growth performance, amino acid transport, and cecal microbiota in yellow-feathered chickens.Poultry science · 2026Article
- Compensatory pathways in tryptophan metabolism and immune regulation following IDO inhibition.Molecular biology reports · 2026Review
- Tryptophan metabolism in tumor microenvironment and therapeutic implications.Journal of advanced research · 2026Review
- The Cancer Cell Metabolic Reprogramming Remodels the Tumor Microenvironment: Molecular Mechanisms and Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Metabolic-epigenetic crosstalk in innate immune cell plasticity within the tumor microenvironment.Experimental & molecular medicine · 2026Review
- d-serine as a metabolic immune checkpoint in the tumour microenvironment.EBioMedicine · 2026Article
- Microbial engraftment and immune regulation during fecal microbiota transplantation and immune checkpoint inhibitor therapy.Nature communications · 2026Review
- Cell-Specific Modulation of the Aryl Hydrocarbon Receptor by Kynurenine in Pulmonary Fibrosis Requires Microenvironmental Crosstalk.bioRxiv : the preprint server for biology · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- LC-QQQ serum metabolomics reveals disease-specific metabolic signatures and diagnostic metabolite panels distinguishing polycythaemia vera from secondary polycythaemia.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Dynamic remodeling of amino acid metabolism in tumor-associated macrophages: Fueling immunosuppression, reshaping tumor niches, and unlocking metabolic checkpoints.Journal of advanced research · 2026Review
- Synergistic immunomodulatory combinations induce robust human tolerogenic dendritic cells for antigen-specific regulatory T cell generation.The Journal of pharmacology and experimental therapeutics · 2026Article
- Decoding the microbiome-immune crosstalk in cancer: from mechanisms to therapeutic translation.Biomarker research · 2026Review
- The Tryptophan Paradox: From Microbiome-Mediated Homeostasis to Tumor-Driven Immune Escape.International journal of molecular sciences · 2026Review
- Complement factor B deficiency promotes lung cancer progression via FOS-mediated tryptophan metabolism and immune suppression.Communications medicine · 2026Article
- Functional segregation of HIF-1α and AhR controls NK cell responsiveness under hypoxia.iScience · 2026Article
- The role of L-type amino acid transporter 1 in the pathogenicity ofMicrobiology spectrum · 2026Article
- Metabolic networks in the tumor microenvironment: roles of amino acid and lipid metabolism pathways in cancer progression and therapy.Experimental & molecular medicine · 2026Review
- Targeting the gut microbiota-metabolite-immune axis in cancer immunotherapy: mechanistic interplay, therapeutic strategies, and translational applications-a narrative review.Translational cancer research · 2026Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIndoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan-dioxygenase (TDO) are enzymes catabolizing the essential amino acid tryptophan into kynurenine. Expression of these enzymes is frequently observed in advanced-stage cancers and is associated with poor disease prognosis and immune suppression. Mechanistically, the respective roles of tryptophan shortage and kynurenine production in suppressing immunity remain unclear. Kynurenine was proposed as an endogenous ligand for the aryl hydrocarbon receptor (AHR), which can regulate inflammation and immunity. However, controversy remains regarding the role of AHR in IDO1/TDO-mediated immune suppression, as well as the involvement of kynurenine. In this study, we aimed to clarify the link between IDO1/TDO expression, AHR pathway activation and immune suppression.
methodsAHR expression and activation was analyzed by RT-qPCR and western blot analysis in cells engineered to express IDO1/TDO, or cultured in medium mimicking tryptophan catabolism by IDO1/TDO. In vitro differentiation of naïve CD4
resultsWe confirmed that IDO1/TDO expression activated AHR in HEK-293-E cells, as measured by the induction of AHR target genes. Unexpectedly, AHR was also overexpressed on IDO1/TDO expression. AHR overexpression did not depend on kynurenine but was triggered by tryptophan deprivation. Multiple human tumor cell lines overexpressed
conclusionsTryptophan deprivation sensitizes the AHR pathway by inducing
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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.