Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer.
Nat Commun
; 11(1): 3584, 2020 07 17.
Article
em En
| MEDLINE
| ID: mdl-32681091
ABSTRACT
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).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tamoxifeno
/
Neoplasias da Mama
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Linfócitos T
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Anticorpos Monoclonais Humanizados
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Vorinostat
/
Imunoterapia
Tipo de estudo:
Clinical_trials
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Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article