Figure 6.

Targeting KAT6A sensitizes PD‐L1 immunotherapy in TNBC by decreasing MDSCs recruitment. A) Effects of treatment of KAT6A inhibitor WM‐1119 on SMAD3 acetylation and IL‐6, IL‐22, TNFα, and p‐STAT3 expression in 4T1 cells with a SMAD3 sgRNA. 4T1 cells were transduced with sgRNA resistant WT SMAD3 or the 2KQ mutant. B) Transwell migration analysis of MDSCs recruitment by indicated 4T1 cells treated with or without WM‐1119. C) Treatment scheme for the evaluation of in vivo efficacy of WM1119 in combination with an anti‐PD‐L1 antibody in 4T1 tumor xenografts. The mice were treated with indicated 30 mg kg⁻¹ WM1119 with or without 12.5 mg kg⁻¹ of the anti‐PD‐L1 antibody within 2 weeks following the indicated administration time and frequency. D) Representative BLI images of treated mice on day 21. E) Quantification of the BLI activity in panel (D). F) Quantification of the number of surface lung metastasis in panel (D). G) Kaplan–Meier survival analysis of animals with indicated 4T1 tumors (n = 6). FACS of H) recruited MDSCs, and I) CD4⁺ T cells and J) CD8⁺ T cells in metastatic lung tissues. Data are representative of two or three independent experiments with similar results. Error bars, SEM. *P < 0.05, **P < 0.01, and ***P < 0.001 by paired two‐way Student's t‐test, one‐way ANOVA, or log‐rank analysis.