ArticleOncoimmunology2012
IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan.
Article in Oncoimmunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 225 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
225 citing papers in PubMed, 371 citations in OpenAlex.
- Tryptophan, glutamine, leucine, and micronutrient supplementation improves environmental enteropathy in Zambian adults: a randomized controlled trial.The American journal of clinical nutrition · 2019Trial
- A hydrogel ionic circuit electrical stimulation system to restore denervated muscle following long-gap peripheral nerve injury.Bioactive materials · 2027Article
- Compensatory pathways in tryptophan metabolism and immune regulation following IDO inhibition.Molecular biology reports · 2026Review
- The role of gut microbiota in thyroid cancer: from pathogenesis to diagnosis and treatment.Journal of endocrinological investigation · 2026Review
- Therapeutic remodeling of the tuberculosis granuloma with 1-methyl-D-tryptophan enhances CD8Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Kynurenine Pathway in Tuberculosis: Focus on Immunometabolic Regulation, Compartment-Specific Biology, and Therapeutic Potential.Life (Basel, Switzerland) · 2026Review
- HCellular & molecular biology letters · 2026Article
- Metabolic Alterations in Macrophage Subtypes Propel Immune and Stromal Remodeling in Neurofibroma's Malignant Progression.MedComm · 2026Article
- Gut microbiota-derived metabolites as immune modulators in aging and age-related chronic inflammatory diseases.Ageing research reviews · 2026Review
- Nexus of IDO1/Kynurenine Pathway to T-Cell Exhaustion: Hypoxia-Induced Tryptophan Metabolism in Glioblastoma.Metabolites · 2026Review
- Mechanisms of Metabolic Reprogramming Regulating Immunosuppression in the Gastric Cancer Tumor Microenvironment.Biomolecules · 2026Review
- Why are long-lived plasma cells long-lived?Frontiers in immunology · 2026Review
- The kynurenine pathway in RNA virus infection: immunometabolic control of antiviral defense and viral persistence.Frontiers in immunology · 2026Review
- Regulation of T cell exhaustion and stemness: molecular mechanisms and implications for cancer immunotherapy.Cellular & molecular immunology · 2026Review
- Therapeutic remodeling of the tuberculosis granuloma with 1-methyl-D-tryptophan enhances CD8bioRxiv : the preprint server for biology · 2025Article
- Metabolites as agents and targets for cancer immunotherapy.Nature reviews. Drug discovery · 2025Review
- The role of immune checkpoint molecules in PRRSV-2-induced immune modulation: insights from comparativeJournal of virology · 2025Article
- Tryptophan and IFN-γ Differentially Modulate Cellular Uptake, Intracellular Trafficking, and Gene Expression of Messenger RNA-Loaded Lipid Nanoparticles in Dendritic Cells.bioRxiv : the preprint server for biology · 2025Article
- Indoleamine-2,3-dioxygenase: An important controller in maintaining mesenchymal stem cell-mediated immunomodulatory homeostasis.Acta pharmaceutica Sinica. B · 2025Review
- Indoleamine 2, 3-dioxygenase Regulates the Differentiation of T Lymphocytes to Promote the Growth of Gastric Cancer Cells through the PI3K/Akt/mTOR Pathway.Cell biochemistry and biophysics · 2025Article
165 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Tryptophan catabolism by indoleamine 2,3-dioxygenase (IDO) alters inflammation and favors T-cell tolerance in cancer, but the underlying molecular mechanisms remain poorly understood. The integrated stress response kinase GCN2, a sensor of uncharged tRNA that is activated by amino acid deprivation, is recognized as an important effector of the IDO pathway. However, in a mouse model of inflammatory carcinogenesis, ablation of Gcn2 did not promote resistance against tumor development like the absence of IDO does, implying the existence of additional cancer-relevant pathways that operate downstream of IDO. Addressing this gap in knowledge, we report that the IDO-mediated catabolism of tryptophan also inhibits the immunoregulatory kinases mTOR and PKC-Θ, along with the induction of autophagy. These effects were relieved specifically by tryptophan but also by the experimental agent 1-methyl-D-tryptophan (D-1MT, also known as NLG8189), the latter of which reversed the inhibitory signals generated by IDO with higher potency. Taken together, our results implicate mTOR and PKC-Θ in IDO-mediated immunosuppressive signaling, and they provide timely insights into the unique mechanism of action of D-1MT as compared with traditional biochemical inhibitors of IDO. These findings are important translationally, because they suggest broader clinical uses for D-1MT against cancers that overexpress any tryptophan catabolic enzyme (IDO, IDO2 or TDO). Moreover, they define mTOR and PKC-Θ as candidate pharmacodynamic markers for D-1MT responses in patients recruited to ongoing phase IB/II cancer trials, addressing a current clinical need.
Identifiers
What OpenQuestion holds
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.