|
| Status |
Public on Oct 17, 2016 |
| Title |
Epigenetic targeting of immunocheckpoint PD-L1 by BET bromodomain inhibition |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Epigenetic regulators have emerged as exciting targets for cancer therapy. Additionally, restoration of antitumor immunity by blocking the PD-L1 signaling using antibodies has proven to be beneficial in cancer therapy. Here we show that BET bromodomain inhibition suppresses PD-L1 expression and restores antitumor immunity 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 antitumor cytotoxic T cells. Together, these data demonstrate an epigenetic approach to block PD-L1 signaling to restore antitumor immunity. Given the fact that BET inhibitors have been proven safe with manageable reversible toxicity in clinical trials, our findings indicate that pharmacological BET inhibitors represent a novel treatment strategy for targeting PD-L1 expression.
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| |
|
| Overall design |
RNA-seq for JQ1 treated and shBRD4 knockdown cells with controls
|
| |
|
| Contributor(s) |
Zhu H, Zhang R |
| Citation(s) |
27626654 |
| Submission date |
May 20, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Priyankara J Wickramasinghe |
| E-mail(s) |
priyaw@wistar.org
|
| Phone |
2154956837
|
| Organization name |
The Wistar Institute
|
| Department |
Bioinformatics
|
| Lab |
Genomics
|
| Street address |
3601 Spruce Street
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (4)
|
|
| Relations |
| BioProject |
PRJNA322328 |
| SRA |
SRP075484 |
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