The interplay of epigenetic therapy and immunity in locally recurrent or metastatic estrogen receptor-positive breast cancer: Correlative analysis of ENCORE 301, a randomized, placebo-controlled phase II trial of exemestane with or without entinostat

Yusuke Tomita, Min Jung Lee, Sunmin Lee, Saori Tomita, Saranya Chumsri, Scott Cruickshank, Peter Ordentlich, Jane B. Trepel

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Entinostat, a class I-selective histone deacetylase inhibitor, has shown promising activity in ENCORE 301, a randomized, placebo-controlled, phase II trial of exemestane with or without entinostat in women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on a nonsteroidal aromatase inhibitor. ENCORE 301 showed an 8.3-mo improvement in median overall survival among patients who received entinostat. We investigated the impact of entinostat on immune subsets with CD40, HLA-DR, and immune checkpoint receptor expression analyses in 34 patient blood samples from ENCORE 301. We found that entinostat significantly decreased granulocytic and monocytic MDSCs at cycle 1 day 15. MDSC CD40 was significantly downregulated by entinostat. A significant increase in HLA-DR expression on CD14+ monocytes by entinostat was observed. Entinostat did not impact T-cell subsets or T-cell immune checkpoint receptor expression. Our findings suggest that a significant interplay between this epigenetic regimen and host immune homeostatic mechanisms may impact therapeutic outcome.

Original languageEnglish (US)
Article numbere1219008
JournalOncoImmunology
Volume5
Issue number11
DOIs
StatePublished - Nov 1 2016

Keywords

  • Breast cancer
  • HLA-DR
  • entinostat
  • exemestane
  • histone deacetylase inhibitors
  • immune checkpoint receptor
  • immune subsets
  • monocyte
  • myeloid-derived suppressor cell
  • regulatory T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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