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

Nature Communications
Manuela Terranova-BarberioPamela N Munster

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).

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Citations

Jan 14, 2021·International Journal of Molecular Sciences·Hsing-Ju Wu, Pei-Yi Chu
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Methods Mentioned

BETA
histone acetylation
flow cytometry
flow
acetylation
biopsies

Clinical Trials Mentioned

NCT02395627

Software Mentioned

irRECIST
Prism
BD FACSDiva
GraphPad
CONSORT
BD FACSuite
FlowJo

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