ArticleJournal for immunotherapy of cancer2023
Polycomb repressor complex 2 suppresses interferon-responsive MHC-II expression in melanoma cells and is associated with anti-PD-1 resistance.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 25 citations in OpenAlex.
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- Epigenetic plasticity in cancer drug resistance: mechanistic insights and strategies for therapeutic intervention.Acta pharmacologica Sinica · 2026Review
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- Decoding the breast cancer microenvironment by spatial multi-omics: from architecture to clinical translation.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Established and Emerging Therapies for High-Risk Neuroblastoma.Paediatric drugs · 2026Review
- Molecular reprogramming in cutaneous melanoma: the central role of G9a and EZH2 methyltransferase inhibitors in tumor plasticity, immune evasion, and therapeutic resistance.Frontiers in pharmacology · 2026Review
- Resistance mechanisms and reversal strategies of PD-1/PD-L1 inhibitors in melanoma.Frontiers in pharmacology · 2026Review
- The CpG island methylator phenotype defines an immune-cold and therapy-resistant subtype of cutaneous melanoma.Frontiers in immunology · 2026Article
- EZH2 in Acral Lentiginous Melanoma: Molecular, Epigenetic, and Therapeutic Perspectives.Oncology research · 2026Review
- Machine learning identified extrachromosomal DNA-related 12 gene signatures to predict cancer immunotherapy response.Cancer cell international · 2025Article
- Loss of tumor cell MHC class II drives MAPK inhibitor insensitivity of BRAF-mutant anaplastic thyroid cancers.The Journal of clinical investigation · 2025Article
- Tumor Microenvironmental Dynamics in Shaping Resistance to Therapeutic Interventions in Melanoma: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Uncovering Novel lncRNAs Linked to Melanoma Growth and Migration with CRISPR Inhibition Screening.Cancer research communications · 2025Article
- A silence catalyst: CCL5-mediated intercellular communication in cancer.Archives of toxicology · 2025Review
- Tumor-specific MHC-II guides anthracycline exemption and immunotherapy benefit in breast cancer.Biomarker research · 2025Article
- The Application of Dendritic Cells Vaccines in Tumor Therapy and Their Combination with Biomimetic Nanoparticles.Vaccines · 2025Review
- Dual role of interferon-gamma in the response of melanoma patients to immunotherapy with immune checkpoint inhibitors.Molecular cancer · 2025Review
- Exosomal miR-92a-3p modulates M2 macrophage polarization in colorectal cancer: implications for tumor migration and angiogenesis.Medical oncology (Northwood, London, England) · 2025Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDespite the remarkable success of immunotherapy in treating melanoma, understanding of the underlying mechanisms of resistance remains limited. Emerging evidence suggests that upregulation of tumor-specific major histocompatibility complex-II (tsMHC-II) serves as a predictive marker for the response to anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) therapy in various cancer types. The genetic and epigenetic pathways modulating tsMHC-II expression remain incompletely characterized. Here, we provide evidence that polycomb repressive complex 2 (PRC2)/EZH2 signaling and resulting H3K27 hypermethylation suppresses tsMHC-II.
methodsRNA sequencing data from tumor biopsies from patients with cutaneous melanoma treated with or without anti-PD-1, targeted inhibition assays, and assays for transposase-accessible chromatin with sequencing were used to observe the relationship between EZH2 inhibition and interferon (IFN)-γ inducibility within the MHC-II pathway.
resultsWe find that increased EZH2 pathway messenger RNA (mRNA) expression correlates with reduced mRNA expression of both presentation and T-cell genes. Notably, targeted inhibition assays revealed that inhibition of EZH2 influences the expression dynamics and inducibility of the MHC-II pathway following IFN-γ stimulation. Additionally, our analysis of patients with metastatic melanoma revealed a significant inverse association between PRC2-related gene expression and response to anti-PD-1 therapy.
conclusionsCollectively, our findings demonstrate that EZH2 inhibition leads to enhanced MHC-II expression potentially resulting from improved chromatin accessibility at
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