ArticleExperimental & molecular medicine2023
Single-cell characterization of macrophages in uveal melanoma uncovers transcriptionally heterogeneous subsets conferring poor prognosis and aggressive behavior.
Article in Experimental & molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 27 citations in OpenAlex.
- Syringin disrupts the DLAT/MYC axis to dampen TAM polarization and suppress hepatocellular carcinoma progression.Acta pharmaceutica Sinica. B · 2026Article
- Machine learning identifies glycosphingolipid signature linking immune dysregulation and clinical prognosis in uveal melanoma.Discover oncology · 2026Article
- Single-cell sequencing and network pharmacology coupled with molecular docking and experimental validation reveal the effects of YPFS on macrophages in stage I non-small cell lung cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Losartan Alleviates Chemical Burn-Induced Limbal Stem Cell Deficiency: Repurposing a Venerable Anti-Hypertension Drug.Investigative ophthalmology & visual science · 2026Article
- Integrating multiple key molecules in uveal melanoma to uncover metastatic and immune microenvironment-related gene signatures.International journal of ophthalmology · 2026Article
- Sequential polarization of macrophages: an immunomodulatory strategy for novel bone repair materials.Regenerative biomaterials · 2026Review
- Targeting bromodomain and extra-terminal proteins reprograms macrophages and inhibits breast cancer progression.Frontiers in immunology · 2026Article
- Comprehensive molecular analysis of uveal melanoma identifies targets in tumor-intrinsic and tumor-extrinsic pathways.iScience · 2025Article
- Characterization of Early Metastatic Subpopulations in Uveal Melanoma: Single-Cell Insights Into SPP1+ Cells and Their Interactions With Macrophages.Investigative ophthalmology & visual science · 2025Article
- Repurposed clindamycin suppresses pyroptosis in tumor-associated macrophages through Inhibition of caspase-1.Journal of experimental & clinical cancer research : CR · 2025Article
- The Advance of Single-Cell RNA Sequencing Applications in Ocular Physiology and Disease Research.Biomolecules · 2025Review
- Mapping the role of cytokine signaling at single-cell and structural resolution in uveal melanoma.Genes and immunity · 2025Article
- Development and Validation of an Extracellular Matrix Gene Expression Signature for Prognostic Prediction in Patients with Uveal Melanoma.International journal of molecular sciences · 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
- 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
- Integrating single-cell omics and materials science for uveal melanoma: from mechanistic insights to precision therapeutics.Frontiers in oncology · 2025Review
- Canonical and noncanonical NF-κB signaling in uveal melanoma: mechanisms, microenvironment, and therapeutic modulation.Medical hypothesis, discovery & innovation ophthalmology journal · 2025Review
- Single-cell and bulk transcriptome analysis reveals tumor cell heterogeneity and underlying molecular program in uveal melanoma.Journal of translational medicine · 2024Article
- Article
- Single-cell hdWGCNA reveals metastatic protective macrophages and development of deep learning model in uveal melanoma.Journal of translational medicine · 2024Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uveal melanoma (UM) is the most frequent primary intraocular malignancy with high metastatic potential and poor prognosis. Macrophages represent one of the most abundant infiltrating immune cells with diverse functions in cancers. However, the cellular heterogeneity and functional diversity of macrophages in UM remain largely unexplored. In this study, we analyzed 63,264 single-cell transcriptomes from 11 UM patients and identified four transcriptionally distinct macrophage subsets (termed MΦ-C1 to MΦ-C4). Among them, we found that MΦ-C4 exhibited relatively low expression of both M1 and M2 signature genes, loss of inflammatory pathways and antigen presentation, instead demonstrating enhanced signaling for proliferation, mitochondrial functions and metabolism. We quantified the infiltration abundance of MΦ-C4 from single-cell and bulk transcriptomes across five cohorts and found that increased MΦ-C4 infiltration was relevant to aggressive behaviors and may serve as an independent prognostic indicator for poor outcomes. We propose a novel subtyping scheme based on macrophages by integrating the transcriptional signatures of MΦ-C4 and machine learning to stratify patients into MΦ-C4-enriched or MΦ-C4-depleted subtypes. These two subtypes showed significantly different clinical outcomes and were validated through bulk RNA sequencing and immunofluorescence assays in both public multicenter cohorts and our in-house cohort. Following further translational investigation, our findings highlight a potential therapeutic strategy of targeting macrophage subsets to control metastatic disease and consistently improve the outcome of patients with UM.
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