
BET Bromodomain Inhibition Promotes Anti-tumor Immunity by Suppressing PD-L1 Expression.
Restoration of anti-tumor immunity by blocking PD-L1 signaling through the use of antibodies has proven to be beneficial in cancer therapy. Here, we show that BET bromodomain inhibition suppresses PD-L1 expression and limits tumor progression in ovarian cancer. CD274 (encoding PD-L1) is a direct target of BRD4-mediated gene transcription. In mouse models, treatment with the BET inhibitor JQ1 significantly reduced PD-L1 expression on tumor cells and tumor-associated dendritic cells and macrophages, which correlated with an increase in the activity of anti-tumor cytotoxic T cells. The BET inhibitor limited tumor progression in a cytotoxic T-cell-dependent manner. Together, these data demonstrate a small-molecule approach to block PD-L1 signaling. Given the fact that BET inhibitors have been proven to be safe with manageable reversible toxicity in clinical trials, our findings indicate that pharmacological BET inhibitors represent a treatment strategy for targeting PD-L1 expression.
Duke Scholars
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Related Subject Headings
- Triazoles
- Transcription, Genetic
- Transcription Factors
- Time Factors
- T-Lymphocytes, Cytotoxic
- Proteins
- Nuclear Proteins
- Neoplasms
- Mice, Inbred C57BL
- Immunity
Citation

Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Triazoles
- Transcription, Genetic
- Transcription Factors
- Time Factors
- T-Lymphocytes, Cytotoxic
- Proteins
- Nuclear Proteins
- Neoplasms
- Mice, Inbred C57BL
- Immunity