ArticleCell communication and signaling : CCS2024
Differentiation status determines the effects of IFNγ on the expression of PD-L1 and immunomodulatory genes in melanoma.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Differentiation state affects PD-L1 expression in cutaneous melanoma: a systematic review.Cellular & molecular biology letters · 2026Pooled it
- Exploration and experimental verification of triaptosis-related prognostic genes and cells in gastric cancer.Molecular biology reports · 2026Article
- Targeting IRF1-TRIM21 axis enhances anti-tumor immunity by promoting ubiquitin-mediated degradation of FGL1 in non-small cell lung cancer.Communications biology · 2026Article
- Enhanced IFNy response in dedifferentiated melanoma cells is due to chromatin remodeling as revealed by ATAC-seq.Cell communication and signaling : CCS · 2026Article
- A NIR-Ⅱ-Immunostimulatory nanoplatform rewires immunometabolism to unleash STING-driven antitumor immunity.Journal of nanobiotechnology · 2026Article
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- Dual role of interferon-gamma in the response of melanoma patients to immunotherapy with immune checkpoint inhibitors.Molecular cancer · 2025Review
- Transcriptomic signatures in peripheral CD4Frontiers in immunology · 2025Article
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8 authors.
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Abstract
backgroundMelanoma cells frequently dedifferentiate in response to inflammation which can increase responses to certain cytokines. Interferon-γ (IFNγ) is an integral part of the anti-tumor immune response and can directly induce both differentiational changes and expression of immunosuppressive proteins in melanoma cells. How the differentiation status of melanoma cells affects IFNγ responses remains unclear.
methodsDedifferentiation of melanoma cells was induced via either siRNA or shRNA mediated MITF knockdown and the cells were subsequently treated with IFNγ. Effects of MITF knockdown and IFNγ treatment on gene expression were evaluated via qPCR and RNA sequencing. A Luminex assay was used to analyze the effects of dedifferentiation and IFNγ treatment on cytokine secretion. Effects on PD-L1 protein expression were analyzed via flow cytometry and western blotting. Inhibition of the JAK kinases, NF-κB and STAT3 with small molecule inhibitors, and siRNA mediated knockdown of STAT1 and IRF1 was applied to investigate the molecular mechanism behind IFNγ induced PD-L1 expression in dedifferentiated melanoma cells. The effects of inhibitor treatments and siRNA mediated knockdowns were evaluated via qPCR and western blotting. Bioinformatic analysis of publicly available RNA sequencing data, consisting of 45 patient derived melanoma cell lines, with or without IFNγ treatment, was conducted to assess the generalizability of the in vitro results.
resultsDedifferentiation renders 624Mel melanoma cells hypersensitive to IFNγ stimulation in a context-dependent manner, resulting in non-additive upregulation of IFNγ-induced genes, increased PD-L1 protein expression and amplified secretion of CCL2, CXCL10 and IL-10. Furthermore, the intensified PD-L1 protein expression occurs through the JAK-STAT1-IRF1 axis. Lastly, dedifferentiated patient derived melanoma cell lines showed enhanced inflammatory signaling in response to IFNγ compared to differentiated cells, and tended to have higher PD-L1 expression, associated with increased IRF1 expression and activity.
conclusionsTogether, these findings indicate the existence of a molecular context linking dedifferentiation and IFNγ signaling in melanoma which may lead to immune evasion. Additionally, the variability in PD-L1 expression among MITF
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