ReviewClinical cancer research : an official journal of the American Association for Cancer Research2019
Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan-Kynurenine-Aryl Hydrocarbon Axis.
Review in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 246 papers, 3 of them syntheses 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
246 citing papers in PubMed, 3 syntheses or guidelines pooled it, 372 citations in OpenAlex.
- A Single Exercise Session Elicits a Transient Kynurenine Metabolic Signature in Health and Disease: A Systematic Review and Meta-Analysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Pooled it
- Phytochemical Modulation of the Kynurenine Pathway (KYNP) and Its Emerging Mechanistic Insights into Cancer Progression: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Chemoprophylaxis Effect of EGCG on the Recurrence of Colorectal Cancer: A Systematic Review and Meta-Analysis.Current pharmaceutical design · 2024Pooled it
- Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors.British journal of cancer · 2023Trial
- Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer.Journal for immunotherapy of cancer · 2021Trial
- The influence of low-carbohydrate diets on the metabolic response to androgen-deprivation therapy in prostate cancer.The Prostate · 2021Trial
- Acute exercise impacts AhR and PD-1 levels of CD8European journal of applied physiology · 2021Trial
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Global and specific mechanisms stimulate mistranslation in cancer.Nature cell biology · 2026Article
- Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.Molecular therapy. Nucleic acids · 2026Review
- Spatial habitat radiomics predicts tertiary lymphoid structure status and identifies an IDO1Journal for immunotherapy of cancer · 2026Article
- Vitexin antagonizes the kynurenine pathway via AhR inhibition to reprogram tumor-associated macrophages and enhance antitumor immunity in lung adenocarcinoma.Molecular and cellular biochemistry · 2026Article
- Evidence for the Formation of an Iron(III)-Indolenylperoxo Intermediate During Indole Dioxygenation: Similarities with Heme Dioxygenases.Inorganic chemistry · 2026Article
- The Kynurenine Pathway in Tuberculosis: Focus on Immunometabolic Regulation, Compartment-Specific Biology, and Therapeutic Potential.Life (Basel, Switzerland) · 2026Review
- Metabolic rewiring of the dendritic cell-T cell axis: tumour-derived barriers and therapeutic opportunities.Experimental & molecular medicine · 2026Review
- Editorial Comment on "Stage-Dependent Changes in Kynurenine Pathway Enzyme Expression Suggest Immune-Related Involvement in Bladder Cancer Progression": Rethinking the Tryptophan-Kynurenine Pathway in Urological Cancer Immunotherapy.International journal of urology : official journal of the Japanese Urological Association · 2026Article
- IDO1 Silencing Enhances Cisplatin Sensitivity in Gastric Cancer Cells via Modulation of Apoptosis and Oxidative Stress.Current issues in molecular biology · 2026Article
- Drug Discovery of Allosteric Molecular Glue Degraders (aMGDs): Expanding the Landscape of Targeted Protein Degradation.Journal of medicinal chemistry · 2026Article
- Chimeric Antigen Receptor-Immune Cell-Based Therapies for Clear Cell Renal Cell Carcinoma: Latest Advancements and Directions.Cancers · 2026Review
- The competition of amino acid among tumors, tumor-associated macrophages and T cells based on metabolic reprogramming.iScience · 2026Review
186 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
Significant progress has been made in cancer immunotherapy with checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)-programmed death-ligand 1 signaling pathways. Tumors from patients showing sustained treatment response predominately demonstrate a T cell-inflamed tumor microenvironment prior to, or early on, treatment. Not all tumors with this phenotype respond, however, and one mediator of immunosuppression in T cell-inflamed tumors is the tryptophan-kynurenine-aryl hydrocarbon receptor (Trp-Kyn-AhR) pathway. Multiple mechanisms of immunosuppression may be mediated by this pathway including depletion of tryptophan, direct immunosuppression of Kyn, and activity of Kyn-bound AhR. Indoleamine 2,3-dioxygenase 1 (IDO1), a principle enzyme in Trp catabolism, is the target of small-molecule inhibitors in clinical development in combination with PD-1 checkpoint inhibitors. Despite promising results in early-phase clinical trials in a range of tumor types, a phase III study of the IDO1-selective inhibitor epacadostat in combination with pembrolizumab showed no difference between the epacadostat-treated group versus placebo in patients with metastatic melanoma. This has led to a diminution of interest in IDO1 inhibitors; however, other approaches to inhibit this pathway continue to be considered. Novel Trp-Kyn-AhR pathway inhibitors, such as Kyn-degrading enzymes, direct AhR antagonists, and tryptophan mimetics are advancing in early-stage or preclinical development. Despite uncertainty surrounding IDO1 inhibition, ample preclinical evidence supports continued development of Trp-Kyn-AhR pathway inhibitors to augment immune-checkpoint and other cancer therapies.
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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.