biostudies-literatureZhong MGuangzhou Science, Technology and Innovation CommissionNational Science Foundation of China | Major Research Plan671https://www.ebi.ac.uk/biostudies/studies/S-EPMC9346138biostudies-literatureUnknown13(8)Sustained expression of programmed cell death receptor-1 (PD-1) is correlated with the exhaustion of T cells, and blockade of the PD-1 pathway is an effective immunotherapeutic strategy for treating various cancers. However, response rates are limited, and many patients do not achieve durable responses. Thus, it is important to seek additional strategies that can improve anticancer immunity. Here, we report that the bromodomain and extraterminal domain (BET) inhibitor JQ1 inhibits PD-1 expression in Jurkat T cells, primary T cells, and T-cell exhaustion models. Furthermore, JQ1 dramatically impaired the expression of PD-1 and T-cell immunoglobulin mucin-domain-containing-3 (Tim-3) and promoted the secretion of cytokines in T cells from patients with acute myeloid leukemia (AML). In line wiCell death & diseaseBET bromodomain inhibition rescues PD-1-mediated T-cell exhaustion in acute myeloid leukemia.PMC9346138201807010004, 20180304001782070152, 8177015281770158Lu YLi PChen CLi KWang LLiu XGao RZeng CNie DLiu ZLi YHuang YZhao RChen ZChen SYu ZYu XZhong MfalseBET bromodomain inhibition rescues PD-1-mediated T-cell exhaustion in acute myeloid leukemia.Sustained expression of programmed cell death receptor-1 (PD-1) is correlated with the exhaustion of T cells, and blockade of the PD-1 pathway is an effective immunotherapeutic strategy for treating various cancers. However, response rates are limited, and many patients do not achieve durable responses. Thus, it is important to seek additional strategies that can improve anticancer immunity. Here, we report that the bromodomain and extraterminal domain (BET) inhibitor JQ1 inhibits PD-1 expression in Jurkat T cells, primary T cells, and T-cell exhaustion models. Furthermore, JQ1 dramatically impaired the expression of PD-1 and T-cell immunoglobulin mucin-domain-containing-3 (Tim-3) and promoted the secretion of cytokines in T cells from patients with acute myeloid leukemia (AML). In line wi2022-01-01T00:00:00Z2022 Aug2026-05-28T00:37:45.086Z2025-04-22T16:37:12.896ZS-EPMC93461383591833010.1038/s41419-022-05123-x