ΔNp63 regulates MDSC survival and metabolism in triple negative breast cancer

Triple-negative breast cancer (TNBC) contributes greatly to mortality of breast cancer, demanding new targetable options. We have shown that TNBC patients have high ΔNp63 expression in tumors. However, the function of ΔNp63 in established TNBC is yet to be explored. In current studies, targeting ΔNp63 with inducible CRISPR KO and HDAC inhibitor Quisinostat, showed that ΔNp63 is important for tumor progression and metastasis in established tumors by promoting myeloid-derived suppressor cell (MDSC) survival through TNF-α. Decreasing ΔNp63 levels is associated with decreased CD4+ and FOXP3+ T-cells while increased CD8+ T-cells. RNA-seq analysis indicates that loss of ΔNp63 alters multiple MDSC properties such as lipid metabolism, chemotaxis, migration, and neutrophil degranulation besides survival. We further demonstrated that targeting ΔNp63 sensitizes chemotherapy. Overall, we showed that ΔNp63 reprograms the MDSC mediated immunosuppressive functions in TNBC, highlighting the benefit of targeting ΔNp63 in chemotherapy resistant TNBC.