ArticleJournal of experimental & clinical cancer research : CR2023
L-kynurenine induces NK cell loss in gastric cancer microenvironment via promoting ferroptosis.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 85 citations in OpenAlex.
- Mechanisms of tumor cell evasion from NK cell-mediated killing and advances in NK cell-based cancer immunotherapy.Pharmaceutical science advances · 2026Review
- Reprogramming of cell death in gastric cancer: From molecular mechanisms to therapeutic potential (Review).International journal of molecular medicine · 2026Review
- Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Uric acid enhances tumor stemness in breast cancer cells by upregulating GMPS.Molecular medicine reports · 2026Article
- Chronic Stress Promotes Gastric Cancer Metastasis by Inducing Microbiota-Associated Kynurenine Accumulation and Macrophage Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tryptophan metabolism in tumor microenvironment and therapeutic implications.Journal of advanced research · 2026Review
- Article
- Targeting tryptophan metabolism in breast cancer immunotherapy: Recent advances and future prospects.Translational oncology · 2026Review
- Tumor cell ferroptosis in antitumor immunity and immunotherapy efficacy.Journal for immunotherapy of cancer · 2026Review
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- miR-495-3p promotes chronic obstructive pulmonary disease by activating ferroptosis in lung epithelial cells through regulation of the ETS1/GPX4 axis.Molecular biology reports · 2026Article
- Decoding the spatiotemporal characteristics of ferroptosis: reshaping tumour therapeutic strategies.Experimental hematology & oncology · 2026Review
- AhR-dependent ferroptosis as a therapeutic opportunity to counteract BRAFi-resistance in melanoma.Cell death discovery · 2026Article
- Dietary advanced glycation products combined with chronic restraint stress induced anxiety-like and depression-like behaviors in male mice.NPJ science of food · 2026Article
- Interplay between natural killer cells and ferroptosis: novel insights in tumor immunity and therapeutic potential.Cell communication and signaling : CCS · 2026Review
- Epigenetic and post-translational regulatory networks of ferroptosis in the tumor immune microenvironment.Experimental hematology & oncology · 2026Review
- PRMT3 Drives IDO1-Dependent Radioresistance and Immunosuppression by Promoting Kynurenine Metabolism in Non-Small Cell Lung Cancer.Cancer research · 2026Article
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- Targeting ferroptosis inInternational journal of oncology · 2026Review
- The role and therapeutic potential of nanotechnology-mediated ferroptosis regulation in myelodysplastic syndromes.Frontiers in oncology · 2026Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundNatural killer (NK) cells play a major role in body's fighting against various types of cancers. Their infiltration in the tumor microenvironment (TME) of gastric cancer (GC) are significantly decreased, which has been reported as a robust prognostic marker. However, the causes leading to NK cells loss in GC TME remains poorly understood.
methodsWe constructed a non-contact co-culturing system and humanized xenograft tumor mice model to detect the influence of GC microenvironment on NK-92 or primary human NK cells viability by flow cytometry. Then through using the specific inhibitors for different types of cell death and examining the surrogate markers, we confirmed ferroptosis in NK cells. Inspired by the accidental discoveries, we constructed a NK-92 cell strain with high expression of GPX4 and treated the humanized xenograft tumor mice model with the NK-92 cells.
resultsWe found L-KYN, mainly generated through indoleamine 2, 3-dioxygenase (IDO) from GC cells, impaired NK cells viability in TME. Further analysis revealed L-KYN induced ferroptosis in NK cells via an AHR-independent way. Moreover, we found NK cells with higher GPX4 expression showed resistance to L-KYN induced ferroptosis. Based on this, we generated GPX4 over-expressed NK-92 cells, and found these cells showed therapeutic potential towards GC.
conclusionsOur study revealed a novel mechanism to explain the decline of NK cell number in GC TME. Notably, we also developed a potential immunotherapy strategy, which might be beneficial in clinical treatment in the future.
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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.