ArticleFrontiers in immunology2026
Single-cell landscape of melanoma reveals ETV5-driven C3 ID4
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Malignant melanoma is characterized by marked intratumoral heterogeneity and an immunosuppressive tumor microenvironment (TME), and resistance to immunotherapy remains common. We hypothesized that melanoma contains a poorly differentiated tumor subpopulation characterized by an ETV5-centered transcriptional program and TGF-β-associated intercellular crosstalk, which may contribute to malignant progression and immune evasion. EV-related signaling was explored as a potential, but unvalidated, component of this phenotype. Methods: We performed integrative single-cell transcriptomic analyses of single-cell RNA sequencing (scRNA-seq) data from 10 Stage I/III melanoma specimens to deconvolute the tumor microenvironment and tumor heterogeneity. Analyses included clustering, differential expression, stemness prediction (CytoTRACE), pseudotime trajectory reconstruction, cell-cell communication (CellChat), and transcriptional regulatory network inference (SCENIC). Functional validation was performed using CRISPR/Cas9-mediated ETV5 knockdown, followed by migration, proliferation, apoptosis, and RT-qPCR assays. Results: We identified 10 major cell types and 6 distinct tumor subpopulations. The C3 ID4 Conclusion: Our integrative single-cell analysis identifies C3 ID4
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