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 language | English (US) |
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Article number | e1219008 |
Journal | OncoImmunology |
Volume | 5 |
Issue number | 11 |
DOIs | |
State | Published - 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