2026-06-30T01:54:17Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/137142024-11-29T16:36:23Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Hühn, Daniela author Martí-Rodrigo, Pablo author Mouron, Silvana author Hansel, Catherine author Tschapalda, Kirsten author Porebski, Bartlomiej author Häggblad, Maria author Lidemalm, Louise author Carreras-Puigvert, Jordi author Quintela Fandino, Miguel Angel author Fernandez-Capetillo, Oscar author 2022-01-16 Among 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. Mol Oncol . 2022 Jan;16(1):148-165. 10.1002/1878-0261.13083 1878-0261 Molecular oncology 34392603 http://hdl.handle.net/20.500.12105/13714 BREAST-CANCER PATIENTS Estrogen receptor HLA IMMUNOTHERAPY INFLAMMATION PD-L1 Prolonged estrogen deprivation triggers a broad immunosuppressive phenotype in breast cancer cells.