ArticleTranslational lung cancer research2021
High indoleamine-2,3-dioxygenase 1 (IDO) activity is linked to primary resistance to immunotherapy in non-small cell lung cancer (NSCLC).
Article in Translational lung cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 57 citations in OpenAlex.
- Tryptophan degradation by intestinal Bacteroides induces anti-tumor immunity and limits melanoma growth.Cell reports. Medicine · 2026Article
- Regulation of PD-1PD-L1 Immune Checkpoints by Gut Microbiota Metabolites and Their Clinical Translational Research: A Review.Immunity, inflammation and disease · 2026Review
- Cancer signaling networks in tumor progression and drug resistance: Crosstalk, adaptive reprogramming and therapeutic targeting (Review).Oncology reports · 2026Review
- CAR immune cell therapy strategies and advances for lung cancer.Discover oncology · 2026Review
- Emerging Predictive Biomarkers of Immunotherapy Sensitivity in Patients with Non-Small Cell Lung Cancer.ImmunoTargets and therapy · 2026Review
- Harnessing IDO inhibitors to optimize cancer immunotherapy.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Immune-oncology-microbiome axis in lung cancer: from carcinogenesis to therapy-a narrative review.Translational lung cancer research · 2025Review
- Immunometabolism: The role of gut-derived microbial metabolites in optimising immune response during checkpoint inhibitor therapy.Clinical and translational medicine · 2025Review
- Intestinal metabolites in colitis-associated carcinogenesis: Building a bridge between host and microbiome.Chinese medical journal · 2025Review
- Multi-omics unveils BCAA metabolism markers L-leucine and HMGCS1 as prognostic marker for immunotherapy efficacy in non-small cell lung cancer.Respiratory research · 2025Article
- The aryl hydrocarbon receptor controls IFN-γ-induced immune checkpoints PD-L1 and IDO via the JAK/STAT pathway in lung adenocarcinoma.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Dermatotoxicity of Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer: Current Advances in Mechanistic Insights and Predictive Biomarker Identification.Cancer management and research · 2025Review
- Microbial metabolite-driven immune reprogramming in tumor immunotherapy: mechanisms and therapeutic perspectives.Frontiers in immunology · 2025Review
- Integrated Multi-Omics Approaches for Predicting Immune Checkpoint Inhibitor Response in NSCLC - Insights From Genomics, Proteomics, and Metabolomics.Lung Cancer (Auckland, N.Z.) · 2025Review
- Prognostic and predictive value of IDO expression in metastatic melanoma treated with Ipilimumab.PloS one · 2025Article
- BCAA metabolism in cancer progression and therapy resistance: The balance between fuel and cell signaling.Frontiers in pharmacology · 2025Review
- Unraveling the Role of the Microbiota in Cancer Immunotherapy: A New Frontier.Research (Washington, D.C.) · 2025Review
- The Aryl Hydrocarbon Receptor Controls IFNγ-Induced Immune Checkpoints PD-L1 and IDO via the JAK/STAT Pathway in Lung Adenocarcinoma.bioRxiv : the preprint server for biology · 2024Article
- Increased coexpression of PD-L1 and IDO1 is associated with poor overall survival in patients with NK/T-cell lymphoma.Leukemia · 2024Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetabolic profiling in non-small cell lung cancer (NSCLC) may identify key metabolic vulnerabilities and shows enormous discovery potential. Preclinical studies showed that metabolic rewiring in cancer plays an essential role in modulation of immunotherapy response. However, this situation is understudied in the clinical setting. Therefore, we aimed to evaluate the plasma metabolic profile of immune checkpoint inhibitor (CI) responding versus non-responding NSCLC patients. The aim of this project is to identify potential predictive biomarkers for CI response.
methodsPlasma samples from CI treated NSCLC patients were analysed at baseline and at the first follow up scan by using a broad targeted metabolomics mass spectrometry panel, and were compared to healthy controls. For further validation of identified key alterations high-performance liquid chromatography (HPLC) for tryptophan (Trp) and kynurenine (Kyn) as indicator of IDO-activity was performed.
resultsSixty-seven metabolites were significantly altered in NSCLC patients compared to healthy controls. The metabolic profile of patients with primary CI resistance showed an increase in indoleamine-2,3-dioxygenase (IDO) and a decrease in branched-chain amino acids (BCAA) compared to baseline concentrations. Deregulated IDO activity was validated by additional HPLC measurements, which revealed that baseline Trp levels were predictive for CI response. According to receiver operating characteristic (ROC)-analysis baseline Trp levels ≥49.3 µmol/L predicted disease control at the first follow up scan with a sensitivity of 89% and a specificity of 71%.
conclusionsWe showed that NSCLC patients are characterized by a distinct metabolic profile compared to healthy controls. Moreover, metabolic changes during CI therapy were observed. Of those IDO metabolism seemed to play an important role in primary CI resistance. Trp as a surrogate parameter of IDO activity is a promising biomarker in patients undergoing treatment with CIs and might be a future marker in trials investigating IDO inhibitors.
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