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The expression of PD‐L1 in breast cancer is associated with estrogen receptor negativity, chemoresistance and epithelial‐to‐mesenchymal transition (EMT), all of which are common features of a highly tumorigenic subpopulation of cancer cells termed cancer stem cells (CSCs). Hitherto, the expression and intrinsic role of PD‐L1 in the dynamics of breast CSCs has not been investigated. To address this issue, we used transcriptomic datasets, proteomics and several in vitro and in vivo assays. Expression profiling of a large breast cancer dataset (530 patients) showed statistically significant correlation (p < 0.0001, r = 0.36) between PD‐L1 expression and stemness score of breast cancer. Specific knockdown of PD‐L1 using ShRNA revealed its critical role in the expression of the embryonic stem cell transcriptional factors: OCT‐4A, Nanog and the stemness factor, BMI1. Conversely, these factors could be …