Exhausted T Cell Signature Predicts Immunotherapy Response in ER-positive Breast Cancer

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Jul 19

PMID 32681091

Citations 88

Authors

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

Pamela N Munster

Affiliations

Soon will be listed here.

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 (CD8PD-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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