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

Manuela Terranova-Barberio, Nela Pawlowska, Mallika Dhawan, Mark Moasser, Amy J. Chien, Michelle E. Melisko, Hope Rugo, Roshun Rahimi, Travis Deal, Adil Daud, Michael D. Rosenblum, Scott Thomas and Pamela N. Munster ()
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Manuela Terranova-Barberio: University of California
Nela Pawlowska: University of California
Mallika Dhawan: University of California
Mark Moasser: University of California
Amy J. Chien: University of California
Michelle E. Melisko: University of California
Hope Rugo: University of California
Roshun Rahimi: University of California
Travis Deal: University of California
Adil Daud: University of California
Michael D. Rosenblum: University of California
Scott Thomas: University of California
Pamela N. Munster: University of California

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: 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).

Date: 2020
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DOI: 10.1038/s41467-020-17414-y

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