ArticleBiomarker research2024
BRD4 inhibitor reduces exhaustion and blocks terminal differentiation in CAR-T cells by modulating BATF and EGR1.
Article in Biomarker research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Preclinical advances and mechanistic insights of CAR-T therapy for acute myeloid leukemia: from target iteration to microenvironment regulation.Annals of medicine · 2026Review
- Genetic Anatomy and Ontogenetic Roles of Early Growth Response 1 (Egr1) in Human and Mouse.Development & reproduction · 2026Review
- Mapping Current Research Status and Emerging Frontiers of T-Cell Exhaustion: A Comprehensive Data-Mining-Based Study.Annals of surgical oncology · 2026Article
- Immunological barriers and engineering strategies for CAR-T cell therapy in acute myeloid leukemia.Frontiers in immunology · 2026Review
- PD-L1 on Tumor-Derived Extracellular Vesicles Induces CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Remodeling of the immune microenvironment is linked to adverse outcome in pediatric T cell acute lymphoblastic leukemia.Nature communications · 2025Article
- Recent advances in CAR-MSCs: the new engine of cellular immunotherapy evolution.Journal of hematology & oncology · 2025Review
- Decoding the diagnostic biomarkers of mitochondrial dysfunction related gene variants in pediatric T cell acute lymphoblastic leukemia.Scientific reports · 2025Article
- Gene Signature-Based Prognostic Model for Acute Myeloid Leukemia: The Role ofInternational journal of medical sciences · 2025Article
- High expression of CCL3/CCL4/CCL5/CCR5 promotes exhausted CD8International journal of immunopathology and pharmacologyArticle
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Authors and funding
9 authors.
Funding
Abstract
backgroundExhaustion is a key factor that influences the efficacy of chimeric antigen receptor T (CAR-T) cells. Our previous study demonstrated that a bromodomain protein 4 (BRD4) inhibitor can revise the phenotype and function of exhausted T cells from leukemia patients. This study aims to elucidate the mechanism by which a BRD4 inhibitor reduces CAR-T cell exhaustion using single-cell RNA sequencing (scRNA-Seq).
methodsExhausted CD123-specific CAR-T cells were prepared by co-culture with CD123 antigen-positive MV411 cells. After elimination of MV411 cells and upregulation of inhibitory receptors on the surface, exhausted CAR-T cells were treated with a BRD4 inhibitor (JQ1) for 72 h. The CAR-T cells were subsequently isolated, and scRNA-Seq was conducted to characterize phenotypic and functional changes in JQ1-treated cells.
resultsBoth the proportion of exhausted CD8
conclusionsOur study reveals that a BRD4 inhibitor can reduce CAR-T cell exhaustion and block exhausted T cell terminal differentiation by downregulating BATF activity and expression together with upregulating EGR1 activity and expression, presenting an approach for improving the effectiveness of CAR-T cell therapy.
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