ArticleCancer & metabolism2023
Dual inhibition of IDO1/TDO2 enhances anti-tumor immunity in platinum-resistant non-small cell lung cancer.
Article in Cancer & metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed.
- Research progress in metabolic reprogramming and targeting metabolic pathways for clear cell renal cell carcinoma.Genes & diseases · 2026Review
- Compensatory pathways in tryptophan metabolism and immune regulation following IDO inhibition.Molecular biology reports · 2026Review
- Mitochondrial Metabolic Biomarkers in Periodontitis: Discovery and Clinical Validation.International dental journal · 2026Article
- Targeting tryptophan metabolism in breast cancer immunotherapy: Recent advances and future prospects.Translational oncology · 2026Review
- Regulation of PD-1PD-L1 Immune Checkpoints by Gut Microbiota Metabolites and Their Clinical Translational Research: A Review.Immunity, inflammation and disease · 2026Review
- Complement factor B deficiency promotes lung cancer progression via FOS-mediated tryptophan metabolism and immune suppression.Communications medicine · 2026Article
- The Tryptophan Paradox: From Microbiome-Mediated Homeostasis to Tumor-Driven Immune Escape.International journal of molecular sciences · 2026Review
- Emphysema Shapes a Pro-Inflammatory Immune Microenvironment in Pulmonary Adenocarcinoma: A Pilot Immune Transcriptomic Profiling Study.International journal of molecular sciences · 2026Article
- Modulating IDO1 and TDO Inhibition Through Structural Modification of Diaryl Hydroxylamines.ChemMedChem · 2026Article
- Molecular and cellular landscapes of the immune microenvironment and multiomic biomarker-sets in platinum-resistant recurrent ovarian cancers.Journal of ovarian research · 2026Review
- SLC1A5-mediated kynurenine metabolism drives AHR-FANCD2 axis to remodel chromatin and induce T cell exhaustion in lung adenocarcinoma.Cell communication and signaling : CCS · 2026Article
- Targeting Overexpressed IDO in Stromal Cells as a Potential Therapeutic Strategy in Multiple Myeloma.Cancer science · 2026Article
- Extracellular Metabolites and Natural Killer Cell Antitumor Function: Mechanisms and Therapeutic Strategies.Research (Washington, D.C.) · 2026Review
- Tryptophan metabolism in tumor immune escape: mechanisms, cellular crosstalk, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Association of IL4I1Frontiers in immunology · 2026Article
- A Review of Aryl Hydrocarbon Receptor-Mediated Immune Regulation in Cutaneous Squamous Cell Carcinoma Progression.ImmunoTargets and therapy · 2026Review
- Spatially resolved tryptophan-kynurenine niches in HNSCC: immunometabolic microdomains and therapeutic implications.Frontiers in immunology · 2026Review
- Targeting MDSCs in cancer: emerging immunotherapeutic and metabolic strategies.Frontiers in immunology · 2026Review
- Understanding the immunomodulatory mechanisms for natural products that overcome tumor chemoresistance to platinum-based cancer drugs and other treatments.Frontiers in pharmacology · 2026Review
- PRMT3 in cancer: arginine methylation as a driver of tumor metabolism, immune evasion, and therapeutic resistance.Frontiers in immunology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
backgroundThe impact of non-small cell lung cancer (NSCLC) metabolism on the immune microenvironment is not well understood within platinum resistance. We have identified crucial metabolic differences between cisplatin-resistant (CR) and cisplatin-sensitive (CS) NSCLC cells with elevated indoleamine 2,3-dioxygenase-1 (IDO1) activity in CR, recognized by increased kynurenine (KYN) production.
methodsCo-culture, syngeneic, and humanize mice models were utilized. C57BL/6 mice were inoculated with either Lewis lung carcinoma mouse cells (LLC) or their platinum-resistant counterpart (LLC-CR) cells. Humanized mice were inoculated with either A (human CS cells) or ALC (human CR cells). Mice were treated with either IDO1 inhibitor or TDO2 (tryptophan 2,3-dioxygenase-2) inhibitor at 200 mg/kg P.O. once a day for 15 days; or with a new-in-class, IDO1/TDO2 dual inhibitor AT-0174 at 170 mg/kg P.O. once a day for 15 days with and without anti-PD1 antibody (10 mg/kg, every 3 days). Immune profiles and KYN and tryptophan (TRP) production were evaluated.
resultsCR tumors exhibited a more highly immunosuppressive environment that debilitated robust anti-tumor immune responses. IDO1-mediated KYN production from CR cells suppressed NKG2D on immune effector natural killer (NK) and CD8
conclusionOur study reports the presence of platinum-resistant lung tumors that utilize both IDO1/TDO2 enzymes for survival, and to escape immune surveillance as a consequence of KYN metabolites. We also report early in vivo data in support of the potential therapeutic efficacy of the dual IDO1/TDO2 inhibitor AT-0174 as a part of immuno-therapeutic treatment that disrupts tumor metabolism and enhances anti-tumor 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.