ArticleCancers2023
Amino Acid-Metabolizing Enzymes in Advanced High-Grade Serous Ovarian Cancer Patients: Value of Ascites as Biomarker Source and Role for IL4I1 and IDO1.
Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Transcriptome-driven constraint-based modelling reveals metabolic targets for ovarian cancer.Cancer & metabolism · 2026Article
- Proteomic analysis of ovarian carcinoma reveals diagnostic and prognostic biomarkers with histotype- and stage-specificity.Journal of ovarian research · 2026Article
- Immune heterogeneity and therapeutic resistance in gynecological malignancies.Frontiers in immunology · 2026Review
- Clinical study on the screening of biomarkers for Crohn's disease based on blood metabolomics.Frontiers in gastroenterology (Lausanne, Switzerland) · 2026Article
- Harnessing ovarian cancer ascites for translational science: models, biomarkers, and therapeutics.Molecular cancer · 2025Review
- Autophagy disruption primes CAR-T cell metabolism for sustained rejection of ovarian tumors.bioRxiv : the preprint server for biology · 2025Article
- Liquid biopsy in gynecological cancers: a translational framework from molecular insights to precision oncology and clinical practice.Journal of experimental & clinical cancer research : CR · 2025Review
- Metabolomic Profiling of Disease Progression Following Radiotherapy for Breast Cancer.Cancers · 2025Article
- Amitriptyline revitalizes ICB response via dually inhibiting Kyn/Indole and 5-HT pathways of tryptophan metabolism in ovarian cancer.iScience · 2024Article
- The Complex World of Kynurenic Acid: Reflections on Biological Issues and Therapeutic Strategy.International journal of molecular sciences · 2024Review
- Claudin-4 Modulates Autophagy via SLC1A5/LAT1 as a Mechanism to Regulate Micronuclei.Cancer research communications · 2024Article
- Liquid biopsy techniques and lung cancer: diagnosis, monitoring and evaluation.Journal of experimental & clinical cancer research : CR · 2024Review
- Implication of fibroblast growth factor 7 in ovarian cancer metastases and patient survival.Frontiers in oncology · 2024Article
- Increased peritoneal TGF-β1 is associated with ascites-induced NK-cell dysfunction and reduced survival in high-grade epithelial ovarian cancer.Frontiers in immunology · 2024Article
- Targeting amino acid-metabolizing enzymes for cancer immunotherapy.Frontiers in immunology · 2024Review
- Tryptophan metabolism enzymes are potential targets in ovarian clear cell carcinoma.Cancer medicine · 2023Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The molecular mechanisms contributing to immune suppression in ovarian cancer are not well understood, hampering the successful application of immunotherapy. Amino acid-metabolizing enzymes are known to contribute to the immune-hostile environment of various tumors through depletion of amino acids and production of immunosuppressive metabolites. We aimed to collectively evaluate the activity of these enzymes in high-grade serous ovarian cancer patients by performing targeted metabolomics on plasma and ascites samples. Whereas no indication was found for enhanced l-arginine or l-glutamine metabolism by immunosuppressive enzymes in ovarian cancer patients, metabolism of l-tryptophan by indoleamine 2,3-dioxygenase 1 (IDO1) was significantly elevated compared to healthy controls. Moreover, high levels of l-phenylalanine- and l-tyrosine-derived metabolites associated with interleukin 4 induced 1 (IL4I1) activity were found in ovarian cancer ascites samples. While l-tryptophan is a major substrate of both IDO1 and IL4I1, only its enhanced conversion into l-kynurenine by IDO1 could be detected, despite the observed activity of IL4I1 on its other substrates. In ascites of ovarian cancer patients, metabolite levels were higher compared to those in plasma, demonstrating the value of utilizing this fluid for biomarker identification. Finally, elevated metabolism of l-phenylalanine and l-tyrosine by IL4I1 correlated with disease stage, pointing towards a potential role for IL4I1 in ovarian cancer progression.
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