Estrogen deprivation triggers an immunosuppressive phenotype in breast cancer cells
| Autor: | Daniela Hühn, Pablo Martí-Rodrigo, Silvana Mouron, Catherine S. Hansel, Kirsten Tschapalda, Bartlomiej Porebski, Maria Häggblad, Louise Lidemalm, Miguel A. Quintela-Fandino, Jordi Carreras-Puigvert, Oscar Fernandez-Capetillo |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
medicine.drug_class business.industry Estrogen receptor Antiestrogen medicine.disease 3. Good health Metastasis 03 medical and health sciences 0302 clinical medicine Immune system Cell killing Breast cancer Estrogen 030220 oncology & carcinogenesis Cancer research medicine Hormonal therapy business skin and connective tissue diseases hormones hormone substitutes and hormone antagonists 030304 developmental biology |
| DOI: | 10.1101/715136 |
| Popis: | Estrogen receptor (ER)-positive breast tumors are routinely treated with estrogen-depriving therapies. Despite their effectiveness, patients often progress into a more aggressive form of the disease. Through a chemical screen oriented to identify chemicals capable of inducing the expression of the immune-checkpoint ligand PD-L1, we found antiestrogens as hits. Subsequent validations confirmed that estrogen deprivation or ERα depletion induces PD-L1 expression in ER-positive breast cancer cells, both in vitro and in vivo. Likewise, PD-L1 expression is increased in metastasis arising from breast cancer patients receiving adjuvant hormonal therapy for their local disease. Transcriptome analyses indicate that estrogen deprivation triggers a broad immunosuppressive program, not restricted to PD-L1. Accordingly, estrogen deprived MCF7 cells are resistant to T-cell mediated cell killing, in a manner that can be reverted by estradiol. Our study reveals that while antiestrogen therapies effectively limit tumor growth in ER-positive breast cancers, they also trigger a transcriptional program that favors immune evasion. |
| Databáze: | OpenAIRE |
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