ArticleCancer research communications2024
EZH2 Inhibition Promotes Tumor Immunogenicity in Lung Squamous Cell Carcinomas.
Article in Cancer research communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 21 citations in OpenAlex.
- Targeting the DNA Damage Response in Cancer.MedComm · 2026Review
- EZH1/2 inhibition improves immunotherapy response through MHC Class II de-repression and neutrophil reprogramming.bioRxiv : the preprint server for biology · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- EZH2 Regulates the Proliferation-Senescence Balance and Tumor-Stromal Signaling in Lung Adenocarcinoma.International journal of molecular sciences · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Methionine restriction for cancer therapy: From preclinical studies to clinical trials.Cancer pathogenesis and therapy · 2026Review
- Lineage plasticity: a new dilemma in lung cancer treatment.Molecular biology reports · 2026Review
- Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: Efficacy, Real-World Outcomes, and the Search for Predictive Biomarkers.Current oncology (Toronto, Ont.) · 2026Review
- Article
- 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
- Epigenetic drugs in cancer therapy: mechanisms, immune modulation, and therapeutic applications.Molecular biomedicine · 2025Review
- Monoclonal antibody immune therapy response instrument for stratification and cost-effective personalized approaches in 3PM-guided pan cancer management.The EPMA journal · 2025Review
- Epigenetic control of antigen presentation failure in osteosarcoma: from single-cell chromatin maps to therapeutic strategies.Frontiers in immunology · 2025Review
- Tumor Heterogeneity and Plasticity in Small Cell Lung Cancer.Lung Cancer (Auckland, N.Z.) · 2025Review
- Lung cancer organoid-based drug evaluation models and new drug development application trends.Translational lung cancer research · 2024Review
- Therapeutic potential of tumor-infiltrating lymphocytes in non-small cell lung cancer.Cancer letters · 2024Review
- Methionine Restriction Reduces Lung Cancer Progression and Increases Chemotherapy Response.bioRxiv : the preprint server for biology · 2024Article
- Cancer mutationscape: revealing the link between modular restructuring and intervention efficacy among mutations.NPJ systems biology and applications · 2024Article
- Pancreatic cancer mutationscape: revealing the link between modular restructuring and intervention efficacy amidst common mutations.bioRxiv : the preprint server for biology · 2024Article
- The role of histone post-translational modifications in cancer and cancer immunity: functions, mechanisms and therapeutic implications.Frontiers in immunology · 2024Review
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Authors and funding
14 authors at 3 institutions in 1 country.
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Abstract
Two important factors that contribute to resistance to immune checkpoint inhibitors (ICI) are an immune-suppressive microenvironment and limited antigen presentation by tumor cells. In this study, we examine whether inhibition of the methyltransferase enhancer of zeste 2 (EZH2) can increase ICI response in lung squamous cell carcinomas (LSCC). Our in vitro experiments using two-dimensional human cancer cell lines as well as three-dimensional murine and patient-derived organoids treated with two inhibitors of the EZH2 plus IFNγ showed that EZH2 inhibition leads to expression of both MHC class I and II (MHCI/II) expression at both the mRNA and protein levels. Chromatin immunoprecipitation sequencing confirmed loss of EZH2-mediated histone marks and gain of activating histone marks at key loci. Furthermore, we demonstrate strong tumor control in models of both autochthonous and syngeneic LSCC treated with anti-PD1 immunotherapy with EZH2 inhibition. Single-cell RNA sequencing and immune cell profiling demonstrated phenotypic changes toward more tumor suppressive phenotypes in EZH2 inhibitor-treated tumors. These results indicate that EZH2 inhibitors could increase ICI responses in patients undergoing treatment for LSCC. SIGNIFICANCE: The data described here show that inhibition of the epigenetic enzyme EZH2 allows derepression of multiple immunogenicity factors in LSCC, and that EZH2 inhibition alters myeloid cells in vivo. These data support clinical translation of this combination therapy for treatment of this deadly tumor type.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.