ArticleJournal of immunology (Baltimore, Md. : 1950)2011
IDO induces expression of a novel tryptophan transporter in mouse and human tumor cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- The role of abnormal amino acid metabolism in the occurrence and development of tumors.Frontiers in oncology · 2026Review
- Metabolites associated with type 2 diabetes and Alzheimer's disease trigger differential intracellular signaling responses in mouse primary neurons.Brain research · 2025Article
- The Kynurenine Pathway and Indole Pathway in Tryptophan Metabolism Influence Tumor Progression.Cancer medicine · 2025Review
- Review
- The Complex World of Kynurenic Acid: Reflections on Biological Issues and Therapeutic Strategy.International journal of molecular sciences · 2024Review
- The high-affinity tryptophan uptake transport system in human cells.Biochemical Society transactions · 2024Review
- Differential responses of primary neuron-secreted MCP-1 and IL-9 to type 2 diabetes and Alzheimer's disease-associated metabolites.Scientific reports · 2024Article
- Discovery of the sEH Inhibitor Epoxykynin as a Potent Kynurenine Pathway Modulator.Journal of medicinal chemistry · 2024Article
- Enhancing Leukemia Treatment: The Role of Combined Therapies Based on Amino Acid Starvation.Cancers · 2024Review
- Differential responses of primary neuron-secreted MCP-1 and IL-9 to type 2 diabetes and Alzheimer's disease-associated metabolites.bioRxiv : the preprint server for biology · 2023Article
- Tryptophan-Starved Human Cells Overexpressing Tryptophanyl-tRNA Synthetase Enhance High-Affinity Tryptophan Uptake via Enzymatic Production of Tryptophanyl-AMP.International journal of molecular sciences · 2023Article
- Prevention and Health Benefits of Prebiotics, Probiotics and Postbiotics in Acute Lymphoblastic Leukemia.Microorganisms · 2023Review
- Nanoengineered drug delivery in cancer immunotherapy for overcoming immunosuppressive tumor microenvironment.Drug delivery and translational research · 2023Review
- Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.Journal of hematology & oncology · 2023Review
- Unveiling tumor immune evasion mechanisms: abnormal expression of transporters on immune cells in the tumor microenvironment.Frontiers in immunology · 2023Review
- Tryptophan metabolism and disposition in cancer biology and immunotherapy.Bioscience reports · 2022Article
- Identification of a Novel Pseudo-Natural Product Type IV IDO1 Inhibitor Chemotype.Angewandte Chemie (International ed. in English) · 2022Article
- Targeting immunometabolism mediated by the IDO1 Pathway: A new mechanism of immune resistance in endometrial cancer.Frontiers in immunology · 2022Review
- Review
- Tryptophan: A Rheostat of Cancer Immune Escape Mediated by Immunosuppressive Enzymes IDO1 and TDO.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
IDO is the rate-limiting enzyme in the kynurenine pathway, catabolizing tryptophan to kynurenine. Tryptophan depletion by IDO-expressing tumors is a common mechanism of immune evasion inducing regulatory T cells and inhibiting effector T cells. Because mammalian cells cannot synthesize tryptophan, it remains unclear how IDO(+) tumor cells overcome the detrimental effects of local tryptophan depletion. We demonstrate that IDO(+) tumor cells express a novel amino acid transporter, which accounts for ∼50% of the tryptophan uptake. The induced transporter is biochemically distinguished from the constitutively expressed tryptophan transporter System L by increased resistance to inhibitors of System L, resistance to inhibition by high concentrations of most amino acids tested, and high substrate specificity for tryptophan. Under conditions of low extracellular tryptophan, expression of this novel transporter significantly increases tryptophan entry into IDO(+) tumors relative to tryptophan uptake through the low-affinity System L alone, and further decreases tryptophan levels in the microenvironment. Targeting this additional tryptophan transporter could be a way of pharmacological inhibition of IDO-mediated tumor escape. These findings highlight the ability of IDO-expressing tumor cells to thrive in a tryptophan-depleted microenvironment by expressing a novel, highly tryptophan-specific transporter, which is resistant to inhibition by most other amino acids. The additional transporter allows tumor cells to strike the ideal balance between supply of tryptophan essential for their own proliferation and survival, and depleting the extracellular milieu of tryptophan to inhibit T cell proliferation.
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Registered trials
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