The programmed death-ligand 1 (PD-L1) expression by tumors results in potent antitumor immune suppression through binding to programmed death-1 (PD-1) on T cells and subsequent inhibition of T cells activity. Although recent pathological studies have shown that PD-L1 is actively expressed in certain ERR-negative breast cancer, little is known about whether ER signaling regulates PD-L1 gene expression. Here, we investigated the relationship between ER alpha and PD-L1 in breast cancer. Analysis of Comprehensive Cell Line Encyclopedia (CCLE) data showed that the average mRNA level of PD-L1 in ER alpha-positive breast cancer cell lines was significantly lower than that in ER alpha-negative breast cancer cell lines. E2 treatment inhibited PD-L1 mRNA expression in hormone-depleted ERR-positive MCF7 cells. Moreover, ectopic expression of ER alpha in triple-negative MDA-MB-231 cells reduced PD-L1 mRNA and protein expression. Consistently, analysis of The Cancer Genome Atlas (TCGA) data revealed an inverse correlation between ERa and PD-L1 expression in ER alpha-positive breast cancer. Taken together, our results identify ER alpha as a negative regulator of PD-L1 gene transcription in breast cancer cells, suggesting that ER alpha loss-of-function may facilitate the immune evasion of breast cancer cells via up-regulation of PD-L1. (C) 2018 Elsevier Inc. All rights reserved.