ArticleCancer immunology, immunotherapy : CII2016
Non-small-cell lung cancer-induced immunosuppression by increased human regulatory T cells via Foxp3 promoter demethylation.
Article in Cancer immunology, immunotherapy : CII, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 36 citations in OpenAlex.
- Ethyl Acetate Extract from Wenxia Formula (WFEA) Attenuates Immunosuppression in Lung Cancer by Inhibiting Treg DifferentiationCurrent topics in medicinal chemistry · 2026Article
- Beyond Foxp3 and TSDR: a dual epigenetic lock framework for treg stability and plasticity.Frontiers in immunology · 2026Review
- Unlocking Lung Cancer Cell Dormancy: An Epigenetic Perspective.International journal of molecular sciences · 2025Review
- The epigenetic hallmarks of immune cells in cancer.Molecular cancer · 2025Review
- Unlocking the potential of T-cell metabolism reprogramming: Advancing single-cell approaches for precision immunotherapy in tumour immunity.Clinical and translational medicine · 2024Review
- Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Inflammatory Cytokine: An Attractive Target for Cancer Treatment.Biomedicines · 2022Review
- LATPS, a novel prognostic signature based on tumor microenvironment of lung adenocarcinoma to better predict survival and immunotherapy response.Frontiers in immunology · 2022Article
- Systematic pan-cancer analysis of the nicotinamide n-methyltransferase in human cancer.Frontiers in genetics · 2022Article
- Identification of Tumor Microenvironment and DNA Methylation-Related Prognostic Signature for Predicting Clinical Outcomes and Therapeutic Responses in Cervical Cancer.Frontiers in molecular biosciences · 2022Article
- Inhibition of galectin-3 augments the antitumor efficacy of PD-L1 blockade in non-small-cell lung cancer.FEBS open bio · 2021Article
- KRAB-ZFP Transcriptional Regulators Acting as Oncogenes and Tumor Suppressors: An Overview.International journal of molecular sciences · 2021Review
- Phosphorylation of SMAD3 in immune cells predicts survival of patients with early stage non-small cell lung cancer.Journal for immunotherapy of cancer · 2021Article
- Role of Methylation in Pro- and Anti-Cancer Immunity.Cancers · 2021Review
- Targeting the epigenetic regulation of antitumour immunity.Nature reviews. Drug discovery · 2020Review
- SUV39H1-DNMT3A-mediated epigenetic regulation of Tim-3 and galectin-9 in the cervical cancer.Cancer cell international · 2020Article
- Independent prognostic value of HIF-1α expression in radiofrequency ablation of lung cancer.Oncology letters · 2020Article
- Ectonucleotidase CD39 and Checkpoint Signalling Receptor Programmed Death 1 are Highly Elevated in Intratumoral Immune Cells in Non-small-cell Lung Cancer.Translational oncology · 2020Article
- Scientific reports concerning the impact of interleukin 4, interleukin 10 and transforming growth factor β on cancer cells.Central-European journal of immunology · 2019Review
- Resistance to Radiotherapy and PD-L1 Blockade Is Mediated by TIM-3 Upregulation and Regulatory T-Cell Infiltration.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with non-small-cell lung cancer (NSCLC) have immune defects that are poorly understood. Forkhead box protein P3 (Foxp3) is crucial for immunosuppression by CD4(+) regulatory T cells (Tregs). It is not well known how NSCLC induces Foxp3 expression and causes immunosuppression in tumor-bearing patients. Our study found a higher percentage of CD4(+) Tregs in the peripheral blood of NSCLC compared with healthy donors. NSCLC patients showed demethylation of eight CpG sites within the Foxp3 promoter with methylation ratios negatively correlated with CD4(+)CD25(+)Foxp3(+) T levels. Foxp3 expression in CD4(+) Tregs was directly regulated by Foxp3 promoter demethylation and was involved in immunosuppression by NSCLC. To verify the effect of tumor cells on the phenotype and function of CD4(+) Tregs, we established a coculture system using NSCLC cell line and healthy CD4(+) T cells and showed that SPC-A1 induced IL-10 and TGF-β1 secretion by affecting the function of CD4(+) Tregs. The activity of DNA methyltransferases from CD4(+) T was decreased during this process. Furthermore, eight CpG sites within the Foxp3 promoter also appeared to have undergone demethylation. Foxp3 is highly expressed in CD4(+) T cells, and this may be caused by gene promoter demethylation. These induced Tregs are highly immunosuppressive and dramatically inhibit the proliferative activity of naïve CD4(+) T cells. Our study provides one possible mechanism describing Foxp3 promoter demethylation changes by which NSCLC down-regulates immune responses and contributes to tumor progression. Foxp3 represents an important target for NSCLC anti-tumor immunotherapy.
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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.