Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer.
Nat Commun
; 11(1): 3584, 2020 07 17.
Article
in 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).
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tamoxifen
/
Breast Neoplasms
/
T-Lymphocytes
/
Antibodies, Monoclonal, Humanized
/
Vorinostat
/
Immunotherapy
Type of study:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Middle aged
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2020
Document type:
Article
Affiliation country: