ArticleOncoimmunology
DNA methylation of immune checkpoints in the peripheral blood of breast and colorectal cancer patients.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 68 citations in OpenAlex.
- Changes in active DNA demethylation pathway components during neoadjuvant chemotherapy and their prognostic significance in breast cancer.Breast cancer research : BCR · 2026Article
- Poliovirus receptor (PVR) expression as a predictor of relapse in colorectal cancer: bioinformatics and virtual screening.Experimental biology and medicine (Maywood, N.J.) · 2026Article
- Epigenetic modulation of CTCs as a novel therapeutic target in oncology.Molecular and cellular biochemistry · 2026Review
- Blood expression of CTLA-4, PD-1, and PD-L1 as potential prognostic and diagnostic markers for breast cancer: a systematic review.Discover oncology · 2025Article
- TIGIT, as a potential immune checkpoint target for immunotherapy of breast cancer.Medical oncology (Northwood, London, England) · 2025Review
- Expression of VISTA on T cells in patients with cancer colon.Journal of the Egyptian National Cancer Institute · 2025Article
- The clinical potential of PDL-1 pathway and some related micro-RNAs as promising diagnostic markers for breast cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- Resistance mechanisms to immune checkpoint inhibitors: updated insights.Molecular cancer · 2025Review
- The evolution of immune profiling: will there be a role for nanoparticles?Nanoscale horizons · 2024Review
- Circulating tumor cells: from new biological insights to clinical practice.Signal transduction and targeted therapy · 2024Review
- Selective Estrogen Receptor Modulators' (SERMs) Influence onInternational journal of molecular sciences · 2024Article
- The role of the immunosuppressive PD-1/PD-L1 checkpoint pathway in the aging process and age-related diseases.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Peripheral immune cells in metastatic breast cancer patients display a systemic immunosuppressed signature consistent with chronic inflammation.NPJ breast cancer · 2024Article
- Regulation of PD-L1 Expression by YY1 in Cancer: Therapeutic Efficacy of Targeting YY1.Cancers · 2024Review
- The level of active DNA demethylation compounds in leukocytes and urine samples as potential epigenetic biomarkers in breast cancer patients.Scientific reports · 2024Article
- TET Enzymes and 5hmC Levels in Carcinogenesis and Progression of Breast Cancer: Potential Therapeutic Targets.International journal of molecular sciences · 2023Review
- Article
- Ezrin regulates the progression of NSCLC by YAP and PD-L1.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Dynamic changes of DNA methylation induced by benzo(a)pyrene in cancer.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2023Review
- Epigenetic and Immunological Features of Bladder Cancer.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant expression of immune checkpoints (ICs) in cancer creates an immunosuppressive microenvironment, which supports immune evasion of tumor cells. We have recently reported that epigenetic modifications are critical for ICs expression in the tumor microenvironment (TME) of primary breast cancer (PBC) and colorectal cancer (CRC). Herein, we investigated transcriptomic expression of ICs (PD-1, CTLA-4, LAG-3, TIM-3, TIGIT) and PD-L1 in peripheral blood of PBC and CRC patients, compared to healthy donors (HD). We found that expressions of TIM-3, TIGIT, PD-L1 were significantly upregulated, while LAG-3 expression was downregulated in peripheral blood of PBC and CRC patients. Demethylation enzymes TET2 and TET3 were also upregulated. In addition, promoter DNA methylation status of PD-1 was significantly hypermethylated, while PD-L1 was hypomethylated in PBC and CRC patients. Furthermore, TIGIT was significantly hypomethylated only in CRC patients. Remarkably, promoter methylation status of LAG-3, TIGIT and PD-L1 was in concordance with transcriptomic expression in CRC: the more the hypomethylation, the higher the expression. In comparison, we found that CTLA-4, TIM-3, TIGIT and PD-L1 in PBC, and CTLA-4 in CRC patients were significantly upregulated in peripheral blood, compared with tumor tissues of the same patients. However, demethylation status of all ICs was higher in TT, except for TIGIT in PBC, and CTLA-4 in CRC patients. These data indicate that the underlying mechanisms behind peripheral upregulation of PD-L1 and TIGIT in cancer patients could be due to aberrant promoter methylation profile. Moreover, demethylation inhibitors together with anti-PD-L1/anti-TIGIT could be a more efficient therapeutic strategy in cancer patients.
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