biostudies-literatureSui SFundamental Research Funds for the Central UniversitiesNatural Science Foundation of ChinaPearl River Talents Scheme of Guangdong Province124https://www.ebi.ac.uk/biostudies/studies/S-EPMC11476310biostudies-literatureUnknown12(1)<h4>Background</h4>Exhaustion 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).<h4>Methods</h4>Exhausted 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 pBiomarker researchBRD4 inhibitor reduces exhaustion and blocks terminal differentiation in CAR-T cells by modulating BATF and EGR1.PMC11476310216231212019QN01Y9908229363281971301Peng XZeng CLuo OJSui SLi YZhong SChen CMao LZhong MfalseBRD4 inhibitor reduces exhaustion and blocks terminal differentiation in CAR-T cells by modulating BATF and EGR1.<h4>Background</h4>Exhaustion 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).<h4>Methods</h4>Exhausted 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 p2024-01-01T00:00:00Z2024 Oct2026-07-15T13:07:22.982Z2025-04-04T07:41:13.266ZS-EPMC114763103940731110.1186/s40364-024-00667-w