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Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer
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Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer
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Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer
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Journal Article
Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer
2020
Overview
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).
ER-positive breast cancer patients do not usually respond to immunotherapy. In this phase II clinical trial, the authors report the safety and efficacy of combining vorinostat and pembrolizumab with tamoxifen in ER-positive breast cancers and provide evidence that T-cell exhaustion may serve as a potential signature for the response of this combination therapy.
