ArticleBlood2019
B-cell-specific IRF4 deletion accelerates chronic lymphocytic leukemia development by enhanced tumor immune evasion.
Article in Blood, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Single mutation tunes IRF4 function and mediates B cell character to ameliorate murine lupus.iScience · 2025Article
- Article
- The chromosomal translocation t(1;6)(p35.3;p25.2), recurrent in chronic lymphocytic leukaemia, leads to RCC1::IRF4 fusion.British journal of haematology · 2024Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- The dynamic functions of IRF4 in B cell malignancies.Clinical and experimental medicine · 2023Review
- CD73 Promotes Chronic Lymphocytic Leukemia.Cancers · 2022Article
- IRF7 inhibits the Warburg effect via transcriptional suppression of PKM2 in osteosarcoma.International journal of biological sciences · 2022Article
- Molecular interactions of IRF4 in B cell development and malignancies.Biophysical reviews · 2021Review
- IRF4 modulates the response to BCR activation in chronic lymphocytic leukemia regulating IKAROS and SYK.Leukemia · 2021Article
- Mouse Models in the Study of Mature B-Cell Malignancies.Cold Spring Harbor perspectives in medicine · 2021Review
- Clonal Evolution of High-Risk Chronic Lymphocytic Leukemia: A Contemporary Perspective.Frontiers in oncology · 2021Review
- Interferon Regulatory Factor 4 Correlated With Immune Cells Infiltration Could Predict Prognosis for Patients With Lung Adenocarcinoma.Frontiers in oncology · 2021Article
- Understanding the Immune-Stroma Microenvironment in B Cell Malignancies for Effective Immunotherapy.Frontiers in oncology · 2021Review
- Notch2 Increases the Resistance to Venetoclax-Induced Apoptosis in Chronic Lymphocytic Leukemia B Cells by Inducing Mcl-1.Frontiers in oncology · 2021Article
- Review
- Identification of Prognostic Immune Genes in Bladder Urothelial Carcinoma.BioMed research international · 2020Article
- Low Humoral Immune Response and Ineffective Clearance of SARS-Cov-2 in a COVID-19 Patient With CLL During a 69-Day Follow-Up.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Chronic lymphocytic leukemia (CLL) is a heterogenous disease that is highly dependent on a cross talk of CLL cells with the microenvironment, in particular with T cells. T cells derived from CLL patients or murine CLL models are skewed to an antigen-experienced T-cell subset, indicating a certain degree of antitumor recognition, but they are also exhausted, preventing an effective antitumor immune response. Here we describe a novel mechanism of CLL tumor immune evasion that is independent of T-cell exhaustion, using B-cell-specific deletion of the transcription factor IRF4 (interferon regulatory factor 4) in Tcl-1 transgenic mice developing a murine CLL highly similar to the human disease. We show enhanced CLL disease progression in IRF4-deficient Tcl-1 tg mice, associated with a severe downregulation of genes involved in T-cell activation, including genes involved in antigen processing/presentation and T-cell costimulation, which massively reduced T-cell subset skewing and exhaustion. We found a strong analogy in the human disease, with inferior prognosis of CLL patients with low IRF4 expression in independent CLL patient cohorts, failed T-cell skewing to antigen-experienced subsets, decreased costimulation capacity, and downregulation of genes involved in T-cell activation. These results have therapeutic relevance because our findings on molecular mechanisms of immune privilege may be responsible for the failure of immune-therapeutic strategies in CLL and may lead to improved targeting in the future.
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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.