CBP/P300 BRD Inhibition Reduces Neutrophil Accumulation and Activates Antitumor Immunity in TNBC

In neutrophil-enriched triple-negative breast cancer (TNBC) models, CREB binding protein (CBP)/P300 bromodomain (BRD) inhibition reduces tumor growth and systemic neutrophil accumulation while stimulating an antitumor immune response. This improves standard-of-care therapies, suggesting a potential therapeutic benefit of CBP/P300 BRD inhibitors for neutrophil-enriched TNBC. For single-cell RNA sequencing of 2208L tumors, the tumors were dissociated and sorted to select live cells. For single-cell RNA-sequencing of bone marrow cells, CD45+/Ter119-/DAPI- cells and lineage-/c-Kit+/CD45+/DAPI- cell were selected and sequenced separately. For both experiments, cells from 3 mice were pooled for each treatment group (vehicle or IACS-70654). The mice were treated for 7 days on a 3-on/2-off schedule.