ArticleHaematologica2013
The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia.
Article in Haematologica, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.
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Who cites it
149 citing papers in PubMed, 1 synthesis or guideline pooled it, 221 citations in OpenAlex.
- Guidelines for Diagnosis and Treatment of Chronic Lymphocytic Leukemia. Krohem B-Cll 2017.Acta clinica Croatica · 2018Guideline
- Ibrutinib treatment improves T cell number and function in CLL patients.The Journal of clinical investigation · 2017Trial
- Phase I-II study of lenalidomide and alemtuzumab in refractory chronic lymphocytic leukemia (CLL): effects on T cells and immune checkpoints.Cancer immunology, immunotherapy : CII · 2017Trial
- c-Medical sciences (Basel, Switzerland) · 2026Review
- Teriflunomide modulates the PD-1/PD-L1 axis and enhances antitumor immunity in colorectal cancer.Oncogenesis · 2026Article
- Advances in Biomarkers for CAR-T Treatment Resistance in Diffuse Large B-Cell Lymphoma.Mini reviews in medicinal chemistry · 2026Review
- Non-Malignant T Cells as Determinants of Immunotherapeutic Response in Chronic Lymphocytic Leukemia: Towards Personalized Strategies.Oncology research · 2026Review
- Association of Galectin-9 Soluble Immune Checkpoint with Clinical Prognostic Markers in Patients with Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2025Article
- Expression of TIM-3 and Gal-9 Immune Checkpoints in Chronic Lymphocytic Leukemia: The Potential Role of Interleukin-27.Current issues in molecular biology · 2025Article
- Article
- Assessment of programmed death ligand 1 (PD-L1) expression in cervical intraepithelial neoplasia and carcinoma cervix.Medical journal, Armed Forces India · 2025Article
- Utilizing miR-34a-Loaded HER2-Targeting Exosomes to Improve Breast Cancer Treatment: Insights From an Animal Model.Journal of breast cancer · 2025Article
- BET Protein Inhibition Relieves MDSC-Mediated Immune Suppression in Chronic Lymphocytic Leukemia.Hemato · 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
- Illuminating the impact of CD38-induced adenosine formation in B-cell lymphoma.Scientific reports · 2025Article
- Impact of mitochondrial metabolism on T-cell dysfunction in chronic lymphocytic leukemia.Frontiers in cell and developmental biology · 2025Review
- A question of TiME: how microenvironmental interactions shape response to immunotherapy in CLL and Richter Transformation.Frontiers in immunology · 2025Review
- PD-1 expression contributes to functional impairment of NK cells in patients with B-CLL.Leukemia · 2024Article
- Determining the relationship of p16Journal of cancer survivorship : research and practice · 2024Article
- NFKBIE mutations are selected by the tumor microenvironment and contribute to immune escape in chronic lymphocytic leukemia.Leukemia · 2024Article
89 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic lymphocytic leukemia is marked by profound defects in T-cell function. Programmed death-1 is a receptor involved in tumor-mediated immunosuppression through binding of the PD-L1 ligand. Multiparametric flow cytometry and immunohistochemistry were used to study PD-1/PD-L1 expression. Functional assays were used to determine the involvement of the PD-1/PD-L1 axis in T-cell responses. PD-1 expression by CD4(+) and CD8(+) T lymphocytes was significantly higher in 117 chronic lymphocytic leukemia patients than in 33 donors of a comparable age. CD4(+) and CD8(+) T lymphocytes from chronic lymphocytic leukemia patients displayed increased numbers of effector memory and terminally differentiated cells, respectively, when compared to controls. The number of effector memory CD4(+) and terminally differentiated CD8(+) lymphocytes positively associated with a more advanced stage of disease, treatment requirements and unfavorable genomic aberrations. Furthermore, leukemic lymphocytes expressed higher levels of PD-L1 than circulating B lymphocytes from normal donors. PD-1 and PD-L1 surface expression spiked in proliferating T and B lymphocytes, suggesting that this interaction works efficiently in activated environments. Within chronic lymphocytic leukemia proliferation centers in the lymph node, CD4(+)/PD-1(+) T lymphocytes were found to be in close contact with PD-L1(+) chronic lymphocytic leukemia cells. Lastly, functional experiments using recombinant soluble PD-L1 and blocking antibodies indicated that this axis contributes to the inhibition of IFN-γ production by CD8(+) T cells. These observations suggest that pharmacological manipulation of the PD-1/PD-L1 axis may contribute to restoring T-cell functions in the chronic lymphocytic leukemia microenvironment.
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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.