ArticleClinical epigenetics2023
CTLA4 DNA methylation is associated with CTLA-4 expression and predicts response to immunotherapy in head and neck squamous cell carcinoma.
Article in Clinical epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Inflammatory markers as prognostic markers in patients with head and neck squamous cell carcinoma treated with immune checkpoint inhibitors: a systematic review and meta-analysis.Frontiers in oncology · 2024Pooled it
- Trial
- Prognostic significance and immune correlation of STING expression and promoter methylation in renal cell carcinoma.Scientific reports · 2026Article
- Targeting epigenetic regulators to boost T cell immunotherapy against cancer.Cell & bioscience · 2026Review
- Promising Targets and Drugs for Improving Head and Neck Cancer Response to Radiotherapy.Current pharmaceutical design · 2026Review
- Association of immune-related gene DNA methylation patterns with tumor progression in colorectal cancer: a clinical translational study.American journal of translational research · 2026Article
- A novel immune-related gene signature stratifies prognosis and characterizes the tumor immune microenvironment in head and neck squamous cell carcinoma.Frontiers in cell and developmental biology · 2026Article
- Review
- DNA methylation profiles predicting response to anti-PD-1-based treatment in patients with advanced gastric cancer.BMC medicine · 2025Article
- Article
- Analysis of a pan-cancer panel reveals the amino acid metabolism-related gene MTHFD1 as a potential prognostic and immunotherapeutic biomarker.Experimental and therapeutic medicine · 2025Article
- TERT promoter methylation predicts overall survival, immune cell infiltration and response to immunotherapy in clear cell renal cell carcinoma.Clinical epigenetics · 2025Article
- High-Sensitivity PD-L1 Staining Using Clone 73-10 Antibody and Spatial Transcriptomics for Precise Expression Analysis in Non-Tumorous, Intraepithelial Neoplasia, and Squamous Cell Carcinoma of Head and Neck.Head and neck pathology · 2025Article
- Immunosuppression and Outcomes in Patients with Cutaneous Squamous Cell Carcinoma of the Head and Neck.Clinics and practice · 2025Article
- Novel Predictive Biomarkers in the Head and Neck Squamous Cell Carcinoma (HNSCC).Journal of clinical medicine · 2024Review
- Identification and validation of a novel risk model based on cuproptosis‑associated m6A for head and neck squamous cell carcinoma.BMC medical genomics · 2024Article
- Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities.Signal transduction and targeted therapy · 2024Review
- Review
- Integrated multiomic analysis reveals disulfidptosis subtypes in glioblastoma: implications for immunotherapy, targeted therapy, and chemotherapy.Frontiers in immunology · 2024Article
- Article
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe majority of patients with recurrent or metastasized head and neck squamous cell carcinoma (HNSCC) do not benefit from immune checkpoint blockade (ICB) while several patients experience severe and persistent immune-mediated side effects. Therefore, predictive biomarkers are urgently needed to allow for a personalized treatment. In this study, we investigated DNA methylation of the immune checkpoint gene CTLA4 with regard to its predictive value.
methodsWe analyzed CTLA4 promoter methylation in tumors of HNSCC patients (N = 29) treated with ICB at the University Medical Center Bonn with regard to response to ICB and progression-free survival. We further analyzed a second cohort (N = 138) of patients that did not receive ICB with regard to CTLA4 promoter methylation, CTLA-4 protein expression, and immune cell infiltrates. Finally, we tested inducibility of CTLA-4 protein expression in HNSCC cells using the DNA methyltransferase inhibitor decitabine.
resultsLower CTLA4 promoter methylation correlated with response to ICB and prolonged progression-free survival. We could show that not only tumor infiltrating immune cells, but also HNSCC cells harbor cytoplasmic and nuclear CTLA-4 expression. CTLA4 promoter methylation inversely correlated with infiltrates of CD3
conclusionsOur results indicate that CTLA4 DNA hypomethylation is a predictive biomarker for response to ICB in HNSCC. Our study warrants further analyses of the predictive value of CTLA4 DNA methylation in clinical trials of anti-PD-1 and/or anti-CTLA-4 immunotherapy in HNSCC.
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Registered trials
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