ArticleJournal for immunotherapy of cancer2022
DNA methylation profiles differ in responders versus non-responders to anti-PD-1 immune checkpoint inhibitors in patients with advanced and metastatic head and neck squamous cell carcinoma.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Peripheral blood DNA methylation profile and immune checkpoint inhibitor response in cancer patients.ESMO open · 2026Article
- DNA methylation profiles predicting response to anti-PD-1-based treatment in patients with advanced gastric cancer.BMC medicine · 2025Article
- Direct genetic transformation bypasses tumor-associated DNA methylation alterations.Genome biology · 2025Article
- Multi-omics in immunotherapy research for HNSCC: present situation and future perspectives.NPJ precision oncology · 2025Review
- Recurrent and Metastatic Head and Neck Cancer: Mechanisms of Treatment Failure, Treatment Paradigms, and New Horizons.Cancers · 2025Review
- DNA Methylation in Lung Cancer: Predictive Biomarkers for Effective Immunotherapy.International journal of general medicine · 2025Review
- The Next Chapter in Cancer Diagnostics: Advances in HPV-Positive Head and Neck Cancer.Biomolecules · 2024Review
- [Molecular pathological analysis through the ages].Pathologie (Heidelberg, Germany) · 2024Review
- DNA Methylation Signatures Correlate with Response to Immune Checkpoint Inhibitors in Metastatic Melanoma.Targeted oncology · 2024Article
- Article
- Current and Emerging Diagnostic, Prognostic, and Predictive Biomarkers in Head and Neck Cancer.Biomedicines · 2024Review
- Refining PD-1/PD-L1 assessment for biomarker-guided immunotherapy: A review.Biomolecules & biomedicine · 2024Review
- Role of DNA Methylation Profiles as Potential Biomarkers and Novel Therapeutic Targets in Head and Neck Cancer.Cancers · 2023Review
- Immunotherapy in Head and Neck Cancer: Where Do We Stand?Current oncology reports · 2023Review
- CTLA4 DNA methylation is associated with CTLA-4 expression and predicts response to immunotherapy in head and neck squamous cell carcinoma.Clinical epigenetics · 2023Article
- DNA Methylation as a Diagnostic, Prognostic, and Predictive Biomarker in Head and Neck Cancer.International journal of molecular sciences · 2023Review
- An integrative multi-omics analysis based on disulfidptosis-related prognostic signature and distinct subtypes of clear cell renal cell carcinoma.Frontiers in oncology · 2023Article
- Design and experimental validation of OPERA_MET-A panel for deep methylation analysis by next generation sequencing.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBiomarkers for response prediction to anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICI) in patients with head and neck squamous cell carcinoma (HNSCC) are urgently needed for a personalized therapy approach. We investigated the predictive potential of inflammatory parameters and DNA methylation profiling in patients with HNSCC treated with anti-PD-1 ICI.
methodsWe identified patients with HNSCC that were treated with anti-PD-1 ICI therapy in the recurrent or metastatic setting after progression to platinum-based chemotherapy in two independent centers. We analyzed DNA methylation profiles of >850.000 CpG sites in tumor specimens of these patients by Infinium MethylationEPIC microarrays, immune cell density in the tumor microenvironment (CD8, CD3, CD45RO, forkhead box P3 (FOXP3), CD68), PD-1 and programmed cell death ligand 1 (PD-L1) expression by immunohistochemistry, and blood inflammation markers (platelet-to-lymphocyte ratio, leucocyte-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio). DNA methylation profiles and immunological markers were bioinformatically and statistically correlated with radiological response to anti-PD-1 ICI.
results37 patients with HNSCC (median age of 62 years; range 49-83; 8 (21.6%) women, 29 (78.4%) men) were included (Center 1 N=26, 70.3%; Center 2 N=11, 29.7%). Median number of prior systemic therapies was 1 (range 1-4). Five out of 37 (13.5%) patients achieved an objective response to ICI. Median progression-free survival and median overall survival times were 3.7 months (range 0-22.9) and 9.0 months (range 0-38.8), respectively. Microarray analyses revealed a methylation signature including both hypomethylation and hypermethylation which was predictive for response to ICI and included several genes involved in cancer-related molecular pathways. Over-represented differentially methylated genes between responders and non-responders were associated with 'Axon guidance', 'Hippo signaling', 'Pathways in cancer' and 'MAPK signaling'. A statistically significant correlation of PD-L1 expression and response was present (p=0.0498).
conclusionsOur findings suggest that tumor DNA methylation profiling may be useful to predict response to ICI in patients with HNSCC.
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