RT Journal Article
SR Electronic
T1 Estrogen deprivation triggers an immunosuppressive phenotype in breast cancer cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 715136
DO 10.1101/715136
A1 Daniela Hühn
A1 Pablo Martí-Rodrigo
A1 Silvana Mouron
A1 Catherine Hansel
A1 Kirsten Tschapalda
A1 Maria Häggblad
A1 Louise Lidemalm
A1 Miguel A. Quintela-Fandino
A1 Jordi Carreras-Puigvert
A1 Oscar Fernandez-Capetillo
YR 2019
UL http://biorxiv.org/content/early/2019/07/25/715136.abstract
AB 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.