دورية أكاديمية
Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer
| العنوان: | Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer |
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| المؤلفون: | 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. |
| المساهمون: | Avon Foundation for Women |
| المصدر: | Nature Communications ; volume 11, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | 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). |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-020-17414-y |
| الإتاحة: | https://doi.org/10.1038/s41467-020-17414-yTest https://www.nature.com/articles/s41467-020-17414-y.pdfTest https://www.nature.com/articles/s41467-020-17414-yTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.4946F555 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-020-17414-y |
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