ArticleJournal of experimental & clinical cancer research : CR2024
Natural killer cells drive 4-1BBL positive uveal melanoma towards EMT and metastatic disease.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Redox Homeostasis, Metabolic Pathways and Plasticity in Uveal Melanoma Compared to Other Cancers.Cancers · 2026Review
- Bioengineering advances in pancreatic cancer organoids for reproducible tumor microenvironment modeling.iScience · 2026Review
- Natural Killer Cell Activation Signature Identifies Cyclin B1/CDK1 as a Druggable Target to Overcome Natural Killer Cell Dysfunction and Tumor Invasiveness in Melanoma.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Transvitreal Retinochoroidal Biopsies of Primary Uveal Melanoma Reveal an Association of Low HLA Class I and High NK Cell Abundance in Low-Risk Disease.Investigative ophthalmology & visual science · 2025Article
- A novel EMT-related risk score model for Uveal melanoma based on ZNF667-AS1 and AP005121.1.Journal of Cancer · 2025Article
- iRGD Tumor Penetrating Peptide-Modified NK Cells Exhibit Enhanced Tumor Immune Infiltration Ability and Anti-Tumor Efficacy.Protein and peptide letters · 2025Article
- Prognostic prediction model for Chinese uveal melanoma patients based on matrix metalloproteinase-2 and -28 expression levels in the tumor.International journal of ophthalmology · 2025Article
- Oxidative stress-related genes in uveal melanoma: the role of CALM1 in modulating oxidative stress and apoptosis and its prognostic significance.Frontiers in oncology · 2025Article
- Immune dynamics shaping pre-metastatic and metastatic niches in liver metastases: from molecular mechanisms to therapeutic strategies.Molecular cancer · 2024Review
- Inhibition of PNCK inflames tumor microenvironment and sensitizes head and neck squamous cell carcinoma to immune checkpoint inhibitors.Journal for immunotherapy of cancer · 2024Article
- Review
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundInflammation in the eye is often associated with aggravated ocular diseases such as uveal melanoma (UM). Poor prognosis of UM is generally associated with high potential of metastatic liver dissemination. A strong driver of metastatic dissemination is the activation of the epithelial-mesenchymal transition (EMT) regulating transcription factor ZEB1, and high expression of ZEB1 is associated with aggressiveness of UM. While ZEB1 expression can be also associated with immune tolerance, the underlying drivers of ZEB1 activation remain unclear.
methodsTranscriptomic, in vitro, ex vivo, and in vivo analyses were used to investigate the impact on clinical prognosis of immune infiltration in the ocular tumor microenvironment. A metastatic liver dissemination model of was developed to address the role of natural killer (NK) cells in driving the migration of UM.
resultsIn a pan-cancer TCGA analysis, natural killer (NK) cells were associated with worse overall survival in uveal melanoma and more abundant in high-risk monosomy 3 tumors. Furthermore, uveal melanoma expressed high levels of the tumor necrosis factor superfamily member 4-1BB ligand, particularly in tumors with monosomy 3 and BAP1 mutations. Tumors expressing 4-1BB ligand induced CD73 expression on NK cells accompanied with the ability to promote tumor dissemination. Through ligation of 4-1BB, NK cells induced the expression of the ZEB1 transcription factor, leading to the formation of liver metastasis of uveal melanoma.
conclusionsTaken together, the present study demonstrates a role of NK cells in the aggravation of uveal melanoma towards metastatic disease.
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