We also show that lineage plasticity in urothelial carcinoma with squamous differentiation is associated with loss of expression of transcription factors critical for maintaining urothelial cell identity and luminal phenotype such as FOXA1, GATA3, and PPARG. By functional analysis, we show that lineage plasticity and PD-L1 expression is coordinately dysregulated via FOXA1 repression. Here, FOXA1 is linked to urothelial carcinoma.