2026-06-30T01:54:21Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/137142024-11-29T16:36:23Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
Karolinska Institutet
funder
Swedish Research Council
funder
Instituto de Salud Carlos III
funder
Unión Europea. Comisión Europea
funder
Comunidad de Madrid (España)
funder
Cancerfonden Foundation
2022-03-03T10:45:44Z
2022-03-03T10:45:44Z
2022-01-16
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
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.
eng
BREAST-CANCER PATIENTS
Estrogen receptor
HLA
IMMUNOTHERAPY
INFLAMMATION
PD-L1
Prolonged estrogen deprivation triggers a broad immunosuppressive phenotype in breast cancer cells.
journal article
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