ArticleOncotarget2016
Phenotypic alteration of CD8+ T cells in chronic lymphocytic leukemia is associated with epigenetic reprogramming.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Review
- Non-Malignant T Cells as Determinants of Immunotherapeutic Response in Chronic Lymphocytic Leukemia: Towards Personalized Strategies.Oncology research · 2026Review
- Predicting Mechanosensitive T Cell Expansion from Cell Spreading.Advanced healthcare materials · 2025Article
- Leveraging the Immunomodulatory Potential of Ibrutinib for Improved Outcomes of T Cell-Mediated Therapies of B Cell Malignancies: A Narrative Review.Targeted oncology · 2025Review
- Normal Residual Lymphoid Cell Populations in Blood as Surrogate Biomarker of the Leukemia Cell Kinetics in CLL BinetA/Rai 0.Cancers · 2025Article
- Assaying and classifying T cell function by cell morphology.BioMedInformatics · 2024Article
- CD20+ T cells in monoclonal B cell lymphocytosis and chronic lymphocytic leukemia: frequency, phenotype and association with disease progression.Frontiers in oncology · 2024Article
- A Cross Sectional Study on T Cells and Subsets in Chronic Lymphocytic Leukemia and their Association with Clinical Phenotype.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2021Article
- Impact of Immune Parameters and Immune Dysfunctions on the Prognosis of Patients with Chronic Lymphocytic Leukemia.Cancers · 2021Review
- Intrinsic Resistance of Chronic Lymphocytic Leukemia Cells to NK Cell-Mediated Lysis Can Be OvercomeFrontiers in immunology · 2021Article
- DNA Methylome Distinguishes Head and Neck Cancer from Potentially Malignant Oral Lesions and Healthy Oral Mucosa.International journal of molecular sciences · 2020Article
- Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance.Cellular oncology (Dordrecht, Netherlands) · 2020Review
- Review
- Immune Response Dysfunction in Chronic Lymphocytic Leukemia: Dissecting Molecular Mechanisms and Microenvironmental Conditions.International journal of molecular sciences · 2020Review
- Immune Dysfunctions and Immune-Based Therapeutic Interventions in Chronic Lymphocytic Leukemia.Frontiers in immunology · 2020Review
- Molecular Interactions Between Innate and Adaptive Immune Cells in Chronic Lymphocytic Leukemia and Their Therapeutic Implications.Frontiers in immunology · 2018Review
- Therapeutic Cancer Vaccines-T Cell Responses and Epigenetic Modulation.Frontiers in immunology · 2018Review
- Higher PD-1 expression concurrent with exhausted CD8+ T cells in patients withChinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2017Article
- Emerging role of BCR signaling inhibitors in immunomodulation of chronic lymphocytic leukemia.Blood advances · 2017Review
- Alterations in DNA methylation/demethylation intermediates predict clinical outcome in chronic lymphocytic leukemia.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
Abstract
Immunosuppression is a prevalent clinical feature in chronic lymphocytic leukemia (CLL) patients, with many patients demonstrating increased susceptibility to infections as well as increased failure of an antitumor immune response. However, much is currently not understood regarding the precise mechanisms that attribute to this immunosuppressive phenotype in CLL. To provide further clarity to this particular phenomenon, we analyzed the T-cell profile of CLL patient samples within a large cohort and observed that patients with an inverted CD4/CD8 ratio had a shorter time to first treatment as well as overall survival. These observations coincided with higher expression of the immune checkpoint receptor PD-1 in CLL patient CD8+ T cells when compared to age-matched healthy donors. Interestingly, we discovered that increased PD-1 expression in CD8+ T cells corresponds with decreased DNA methylation levels in a distal upstream locus of the PD-1 gene PDCD1. Further analysis using luciferase reporter assays suggests that the identified PDCD1 distal upstream region acts as an enhancer for PDCD1 transcription and this region becomes demethylated during activation of naïve CD8+ T cells by anti-CD3/anti-CD28 antibodies and IL2. Finally, we conducted a genome-wide DNA methylation analysis comparing CD8+ T cells from CLL patients against healthy donors and identified additional differentially methylated genes with known immune regulatory functions including CCR6 and KLRG1. Taken together, our findings reveal the occurrence of epigenetic reprogramming taking place within CLL patient CD8+ T cells and highlight the potential mechanism of how immunosuppression is accomplished in CLL.
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