BET inhibition reforms the immune microenvironment and alleviates T-cell dysfunction in chronic lymphocytic leukemia

The pan-BET (bromodomain and extra-terminal) inhibitor, OPN-51107 (OPN5) was found to alleviate features of T-cell exhaustion in models of chronic lymphocytic leukemia (CLL). To evaluate if OPN5 treatment could relieve fixed chromatin states associated with terminal T-cell dysfunction, ATAC-sequencing was performed on CLL patient T-cells. Peripheral blood mononuclear cells (PBMCs) from 4 treatment-naive CLL patients were treated ex vivo with 0.5 uM OPN5 or equivalent vehicle (DMSO) in the presence of T-cell activating stimuli (10 ug/mL anti-CD3 and 5 ug/mL anti-CD28) for 16 hours. Live CD8+ T-cells were then isolated via fluorescence-activated cell sorting, and approximately 100,000 viable CD8+ T-cells were subjected to ATAC-sequencing. Libraries were prepared using the Active Motif... (for more see dbGaP study page.)