Hühn, DanielaMartí-Rodrigo, PabloMouron, SilvanaHansel, CatherineTschapalda, KirstenPorebski, BartlomiejHäggblad, MariaLidemalm, LouiseCarreras-Puigvert, JordiQuintela Fandino, Miguel AngelFernandez-Capetillo, Oscar2022-03-032022-03-032022-01-16Mol Oncol . 2022 Jan;16(1):148-165.http://hdl.handle.net/20.500.12105/13714Among others, expression levels of programmed cell death 1 ligand 1 (PD-L1) have been explored as biomarkers of the response to immune checkpoint inhibitors in cancer therapy. Here, we present the results of a chemical screen that interrogated how medically approved drugs influence PD-L1 expression. As expected, corticosteroids and inhibitors of Janus kinases were among the top PD-L1 downregulators. In addition, we identified that PD-L1 expression is induced by antiestrogenic compounds. Transcriptomic analyses indicate that chronic estrogen receptor alpha (ERα) inhibition triggers a broad immunosuppressive program in ER-positive breast cancer cells, which is subsequent to their growth arrest and involves the activation of multiple immune checkpoints together with the silencing of the antigen-presenting machinery. Accordingly, estrogen-deprived MCF7 cells are resistant to T-cell-mediated cell killing, in a manner that is independent of PD-L1, but which is reverted by estradiol. Our study reveals that while antiestrogen therapies efficiently limit the growth of ER-positive breast cancer cells, they concomitantly trigger a transcriptional program that favors their immune evasion.engVoRhttp://creativecommons.org/licenses/by-nc-sa/4.0/BREAST-CANCER PATIENTSEstrogen receptorHLAIMMUNOTHERAPYINFLAMMATIONPD-L1Atribución-NoComercial-CompartirIgual 4.0 Internacional34392603161148-16510.1002/1878-0261.130831878-0261Molecular oncologyopen access