ArticleProceedings of the National Academy of Sciences of the United States of America2012
Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 303 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
303 citing papers in PubMed, 1 synthesis or guideline pooled it, 566 citations in OpenAlex.
- Tryptophan 2,3-dioxygenase may be a potential prognostic biomarker and immunotherapy target in cancer: A meta-analysis and bioinformatics analysis.Frontiers in oncology · 2022Pooled it
- Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers.Cell death & disease · 2021Trial
- Tryptophan metabolism in tumor microenvironment and therapeutic implications.Journal of advanced research · 2026Review
- The Kynurenine Pathway: Unraveling Its Role in Neurological Disorders via Mammalian Cellular Models.International journal of molecular sciences · 2026Review
- In vivo inhibition of TDO2 in fibroids results in widespread alteration in the tumor transcriptome.Clinical science (London, England : 1979) · 2026Article
- Harnessing myeloid cell plasticity for cancer therapy.Nature cancer · 2026Review
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- The aryl hydrocarbon receptor: structure, signaling, physiology and pathology.Signal transduction and targeted therapy · 2026Review
- Metabolic characteristics in hepatocellular carcinoma: amino acid metabolic reprogramming.Molecular cancer · 2026Review
- 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
- Metabolic Barriers to Cancer Immunotherapy: Multiscale Mechanisms from Organelle Dysfunction to Organ-Specific Constraints.International journal of biological sciences · 2026Review
- Spatially resolved tryptophan-kynurenine niches in HNSCC: immunometabolic microdomains and therapeutic implications.Frontiers in immunology · 2026Review
- Gut microbiota-regulated tryptophan metabolism in breast cancer: mechanisms and therapeutic perspectives.Frontiers in oncology · 2026Review
- Integrated Transcriptomic and Metabolomic Analysis Revealed That Tryptophan Metabolism-Related Metabolites Are Biomarkers of Trastuzumab Resistance.Journal of clinical laboratory analysis · 2025Article
- Is dystrophin immunogenicity a barrier to advancing gene therapy for Duchenne muscular dystrophy?Gene therapy · 2025Review
- Metabolites as agents and targets for cancer immunotherapy.Nature reviews. Drug discovery · 2025Review
- Biomimetic nanoimmunotherapy boosts spatiotemporal PANoptosis and reshapes desmoplastic tumor microenvironment.Cell reports. Medicine · 2025Article
- The aryl hydrocarbon receptor: a rehabilitated target for therapeutic immune modulation.Nature reviews. Drug discovery · 2025Review
- Elevated brain manganese induces motor disease by upregulating the kynurenine pathway of tryptophan metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Advances in tumor subclone formation and mechanisms of growth and invasion.Journal of translational medicine · 2025Review
243 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
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO1) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance, and IDO1 inhibition is an active area of drug development. Tryptophan 2,3-dioxygenase (TDO) is an unrelated hepatic enzyme that also degrades tryptophan along the kynurenine pathway. Here, we show that enzymatically active TDO is expressed in a significant proportion of human tumors. In a preclinical model, TDO expression by tumors prevented their rejection by immunized mice. We developed a TDO inhibitor, which, upon systemic treatment, restored the ability of mice to reject TDO-expressing tumors. Our results describe a mechanism of tumoral immune resistance based on TDO expression and establish proof-of-concept for the use of TDO inhibitors in cancer therapy.
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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.