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Dysregulation of CREB-binding protein (CBP)\/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP\/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a selective CBP\/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP\/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP\/P300 BRD also stimulated the immune response by inducing an IFN response and MHCI expression in tumor cells and increasing tumor-infiltrated cytotoxic T cells. Moreover, IACS-70654 improved the response of a neutrophil-enriched TNBC model to docetaxel and immune checkpoint blockade. 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