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

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 end...

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Autores principales: Terranova-Barberio, Manuela, Pawlowska, Nela, Dhawan, Mallika, Moasser, Mark, Chien, Amy J., Melisko, Michelle E., Rugo, Hope, Rahimi, Roshun, Deal, Travis, Daud, Adil, Rosenblum, Michael D., Thomas, Scott, Munster, Pamela N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367885/
https://www.ncbi.nlm.nih.gov/pubmed/32681091
http://dx.doi.org/10.1038/s41467-020-17414-y
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author Terranova-Barberio, Manuela
Pawlowska, Nela
Dhawan, Mallika
Moasser, Mark
Chien, Amy J.
Melisko, Michelle E.
Rugo, Hope
Rahimi, Roshun
Deal, Travis
Daud, Adil
Rosenblum, Michael D.
Thomas, Scott
Munster, Pamela N.
author_facet Terranova-Barberio, Manuela
Pawlowska, Nela
Dhawan, Mallika
Moasser, Mark
Chien, Amy J.
Melisko, Michelle E.
Rugo, Hope
Rahimi, Roshun
Deal, Travis
Daud, Adil
Rosenblum, Michael D.
Thomas, Scott
Munster, Pamela N.
author_sort Terranova-Barberio, Manuela
collection PubMed
description 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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spelling pubmed-73678852020-07-21 Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer Terranova-Barberio, Manuela Pawlowska, Nela Dhawan, Mallika Moasser, Mark Chien, Amy J. Melisko, Michelle E. Rugo, Hope Rahimi, Roshun Deal, Travis Daud, Adil Rosenblum, Michael D. Thomas, Scott Munster, Pamela N. Nat Commun Article 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). Nature Publishing Group UK 2020-07-17 /pmc/articles/PMC7367885/ /pubmed/32681091 http://dx.doi.org/10.1038/s41467-020-17414-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Terranova-Barberio, Manuela
Pawlowska, Nela
Dhawan, Mallika
Moasser, Mark
Chien, Amy J.
Melisko, Michelle E.
Rugo, Hope
Rahimi, Roshun
Deal, Travis
Daud, Adil
Rosenblum, Michael D.
Thomas, Scott
Munster, Pamela N.
Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer
title Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer
title_full Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer
title_fullStr Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer
title_full_unstemmed Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer
title_short Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer
title_sort exhausted t cell signature predicts immunotherapy response in er-positive breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367885/
https://www.ncbi.nlm.nih.gov/pubmed/32681091
http://dx.doi.org/10.1038/s41467-020-17414-y
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