Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 68, Issue 12, Pages 2081-2094Publisher
SPRINGER
DOI: 10.1007/s00262-019-02430-9
Keywords
Breast cancer; MHC class II; T-cell exhaustion; TCR repertoire; HDAC inhibitor
Categories
Funding
- University of Alabama at Birmingham Comprehensive Cancer Center [P30 CA013148]
- National Institutes of Health [CA216234]
- Breast Cancer Research Foundation of Alabama
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Histone deacetylase (HDAC) inhibitors impair tumor cell proliferation and alter gene expression. However, the impact of these changes on anti-tumor immunity is poorly understood. Here, we showed that the class I HDAC inhibitor, entinostat (ENT), promoted the expression of immune-modulatory molecules, including MHCII, costimulatory ligands, and chemokines on murine breast tumor cells in vitro and in vivo. ENT also impaired tumor growth in vivo-an effect that was dependent on both CD8(+) T cells and IFN gamma. Moreover, ENT promoted intratumoral T-cell clonal expansion and enhanced their functional activity. Importantly, ENT sensitized normally unresponsive tumors to the effects of PD1 blockade, predominantly through increases in T-cell proliferation. Our findings suggest that class I HDAC inhibitors impair tumor growth by enhancing the proliferative and functional capacity of CD8(+) T cells and by sensitizing tumor cells to T-cell recognition.
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