ReviewFrontiers in immunology2021
Tryptophan: A Rheostat of Cancer Immune Escape Mediated by Immunosuppressive Enzymes IDO1 and TDO.
Review in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 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
- Kynurenine metabolism-related gene signature for prognostic stratification in hepatocellular carcinoma.Translational cancer research · 2026Article
- IDO1 Silencing Enhances Cisplatin Sensitivity in Gastric Cancer Cells via Modulation of Apoptosis and Oxidative Stress.Current issues in molecular biology · 2026Article
- Tryptophan degradation by intestinal Bacteroides induces anti-tumor immunity and limits melanoma growth.Cell reports. Medicine · 2026Article
- T cell fate regulation in EBV‑associated nasopharyngeal carcinoma (Review).Oncology reports · 2026Review
- The immunological profile of RC17 hESC-derived dopaminergic neural progenitor cells in vitro: Implications for the STEM-PD clinical trial.Stem cell reports · 2026Article
- Cancer Stemness and Dedifferentiation in Anaplastic Thyroid Carcinoma: Insights into a Multigenic, Microenvironmental Network and the Role of CD44.Biomedicines · 2026Review
- The Bioinformatics and Experimental Analysis of CD276 for Prognosis and Immune Infiltrates in Colon Adenocarcinoma.Cancer reports (Hoboken, N.J.) · 2026Article
- IDO family: the metabolic crossroads connecting immunity, nerves and tumors.Journal of translational medicine · 2026Review
- From immune desert to hot tumor: the tripartite synergy of tumor microenvironment-exosomes-immunogenic cell death in pioneering solutions.Frontiers in immunology · 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
- Immunometabolic Reprogramming in Hepatocellular Carcinoma Mechanisms, Biomarkers, and Therapeutic Implications.Oncology research · 2026Review
- N4-acetylcytidine modification bridges metabolic reprogramming and immune evasion in cancer: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Critical role of reproductive tract microbiota and derived metabolites in inflammation, tumor immunity, and tumorigenesis of gynecological cancers: a narrative review.Frontiers in immunology · 2026Review
- Advances in understanding the tumor microenvironment of neuroendocrine prostate cancer.Frontiers in oncology · 2026Review
- From immune exclusion to exhaustion: tumor microenvironment drives therapy response.Frontiers in immunology · 2026Review
- PRMT3 in cancer: arginine methylation as a driver of tumor metabolism, immune evasion, and therapeutic resistance.Frontiers in immunology · 2026Review
- Microbiome dysbiosis and chemotherapy resistance in acute myeloid leukemia (AML).NPJ biofilms and microbiomes · 2025Review
- Metabolomics of Prostate Cancer and Clinical Profiles Following Radiotherapy: Need for a Precision Phylometabolomics Approach.Diagnostics (Basel, Switzerland) · 2025Article
- Innovative gene engineering and drug delivery systems for dendritic cells in cancer immunotherapy.Journal of biomedical science · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blockade of the immunosuppressive tryptophan catabolism mediated by indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) holds enormous promise for sensitising cancer patients to immune checkpoint blockade. Yet, only IDO1 inhibitors had entered clinical trials so far, and those agents have generated disappointing clinical results. Improved understanding of molecular mechanisms involved in the immune-regulatory function of the tryptophan catabolism is likely to optimise therapeutic strategies to block this pathway. The immunosuppressive role of tryptophan metabolite kynurenine is becoming increasingly clear, but it remains a mystery if tryptophan exerts functions beyond serving as a precursor for kynurenine. Here we hypothesise that tryptophan acts as a rheostat of kynurenine-mediated immunosuppression by competing with kynurenine for entry into immune T-cells through the amino acid transporter called System L. This hypothesis stems from the observations that elevated tryptophan levels in TDO-knockout mice relieve immunosuppression instigated by IDO1, and that the vacancy of System L transporter modulates kynurenine entry into CD4+ T-cells. This hypothesis has two potential therapeutic implications. Firstly, potent TDO inhibitors are expected to indirectly inhibit IDO1 hence development of TDO-selective inhibitors appears advantageous compared to IDO1-selective and dual IDO1/TDO inhibitors. Secondly, oral supplementation with System L substrates such as leucine represents a novel potential therapeutic modality to restrain the immunosuppressive kynurenine and restore anti-tumour immunity.
Indexed as
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.