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Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer

Responses to immunotherapy are uncommon in estrogen receptor (ER)-positive breast cancer and to date, lack predictive markers. This randomized phase II study defines safety and response rate of epigenetic priming in ER-positive breast cancer patients treated with checkpoint inhibitors as primary end...

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Detalles Bibliográficos
Autores principales: Terranova-Barberio, Manuela, Pawlowska, Nela, Dhawan, Mallika, Moasser, Mark, Chien, Amy J., Melisko, Michelle E., Rugo, Hope, Rahimi, Roshun, Deal, Travis, Daud, Adil, Rosenblum, Michael D., Thomas, Scott, Munster, Pamela N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367885/
https://www.ncbi.nlm.nih.gov/pubmed/32681091
http://dx.doi.org/10.1038/s41467-020-17414-y
Descripción
Sumario:Responses to immunotherapy are uncommon in estrogen receptor (ER)-positive breast cancer and to date, lack predictive markers. This randomized phase II study defines safety and response rate of epigenetic priming in ER-positive breast cancer patients treated with checkpoint inhibitors as primary endpoints. Secondary and exploratory endpoints included PD-L1 modulation and T-cell immune-signatures. 34 patients received vorinostat, tamoxifen and pembrolizumab with no excessive toxicity after progression on a median of five prior metastatic regimens. Objective response was 4% and clinical benefit rate (CR + PR + SD > 6 m) was 19%. T-cell exhaustion (CD8(+ )PD-1(+)/CTLA-4(+)) and treatment-induced depletion of regulatory T-cells (CD4(+) Foxp3(+)/CTLA-4(+)) was seen in tumor or blood in 5/5 patients with clinical benefit, but only in one non-responder. Tumor lymphocyte infiltration was 0.17%. Only two non-responders had PD-L1 expression >1%. This data defines a novel immune signature in PD-L1-negative ER-positive breast cancer patients who are more likely to benefit from immune-checkpoint and histone deacetylase inhibition (NCT02395627).