ArticleClinical epigenetics2018
DNA methylation and repressive H3K9 and H3K27 trimethylation in the promoter regions of PD-1, CTLA-4, TIM-3, LAG-3, TIGIT, and PD-L1 genes in human primary breast cancer.
Article in Clinical epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 145 citations in OpenAlex.
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Synergistic Effects of Inflammation and Drug Interactions onPharmaceutics · 2026Article
- Integrated pan-cancer profiling highlights OSR2 as a prognostic indicator and immune-associated biomarker.Discover oncology · 2026Article
- Comprehensive Bioinformatic Characterization of CD70, CD80, and TIGIT as Diagnostic, Prognostic, and Immune Biomarkers in Pan-Cancer.Current issues in molecular biology · 2026Article
- Review
- Stiffness-dependent alveolar type II cell senescence in idiopathic pulmonary fibrosis.Cell communication and signaling : CCS · 2026Article
- The absence of B7-H4 inhibits PD-L1 expression by driving a methylation of PD-L1 promoter in breast cancer cells.Breast cancer research : BCR · 2026Article
- Cancer in transition: discovery of tumor-intrinsic transcriptional programs shaping the immune and microenvironmental landscape.Biomarker research · 2026Review
- Modifying Epigenetic Landscapes to Restore Immune Therapeutic Responses in Triple Negative Breast Cancer.Cancers · 2026Review
- Altered chromatin accessibility and nucleosome positioning landscape upon HDAC and LSD1 inhibition in cancer cell.bioRxiv : the preprint server for biology · 2026Article
- Association of immune-related gene DNA methylation patterns with tumor progression in colorectal cancer: a clinical translational study.American journal of translational research · 2026Article
- Epigenetic crosstalk in neuroblastoma development and progression.Frontiers in cell and developmental biology · 2026Review
- Integrated multi-omics analysis identifies key biomarkers associated with post-translational modifications and RNA methylation in clear cell renal cell carcinoma.Discover oncology · 2025Article
- Epi-Immunotherapy in Cancer Treatment: Mechanisms, Clinical Progress, and Future Directions.Cancer innovation · 2025Review
- TIGIT, as a potential immune checkpoint target for immunotherapy of breast cancer.Medical oncology (Northwood, London, England) · 2025Review
- Epi-nutrients for cancer prevention: Molecular mechanisms and emerging insights.Cell biology and toxicology · 2025Review
- Reprogramming the breast tumor immune microenvironment: cold-to-hot transition for enhanced immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Decoding the Epigenome of Breast Cancer.International journal of molecular sciences · 2025Review
- Assessment of CTLA-4 Gene Expression Levels on CD8+ T Cells in Renal Transplant Patients and Relation with Serum sCTLA-4 Levels.Biochemical genetics · 2025Article
- Resistance mechanisms to immune checkpoint inhibitors: updated insights.Molecular cancer · 2025Review
36 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: High expression of immune checkpoints in tumor microenvironment plays significant roles in inhibiting anti-tumor immunity, which is associated with poor prognosis and cancer progression. Major epigenetic modifications in both DNA and histone could be involved in upregulation of immune checkpoints in cancer. Methods: Expressions of different immune checkpoint genes and PD-L1 were assessed using qRT-PCR, and the underlying epigenetic modifications including CpG methylation and repressive histone abundance were determined using bisulfite sequencing, and histone 3 lysine 9 trimethylation (H3K9me3) and histone 3 lysine 27 trimethylation (H3K27me3) chromatin immunoprecipitation assays (ChIP), respectively. Results: We first assessed the expression level of six immune checkpoints/ligands and found that PD-1, CTLA-4, TIM-3, and LAG-3 were significantly upregulated in breast tumor tissues (TT), compared with breast normal tissues (NT). We investigated the epigenetic modifications beyond this upregulation in immune checkpoint genes. Interestingly, we found that CpG islands in the promoter regions of PD-1, CTLA-4, and TIM-3 were significantly hypomethylated in tumor compared with normal tissues. Additionally, CpG islands of PD-L1 promoter were completely demethylated (100%), LAG-3 were highly hypomethylated (80-90%), and TIGIT were poorly hypomethylated (20-30%), in both NT and TT. These demethylation findings are in accordance with the relative expression data that, out of all these genes, PD-L1 was highly expressed and completely demethylated and TIGIT was poorly expressed and hypermethylated in both NT and TT. Moreover, bindings of H3K9me3 and H3K27me3 were found to be reduced in the promoter loci of PD-1, CTLA-4, TIM-3, and LAG-3 in tumor tissues. Conclusion: Our data demonstrate that both DNA and histone modifications are involved in upregulation of PD-1, CTLA-4, TIM-3, and LAG-3 in breast tumor tissue and these epigenetic modifications could be useful as diagnostic/prognostic biomarkers and/or therapeutic targets in breast cancer.
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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.