Immunogenicity of prostate cancer is augmented by BET bromodomain inhibition.

ABSTRACT:

Background

Prostate cancer responds poorly to current immunotherapies. Epigenetic therapies such as BET Bromodomain inhibition can change the transcriptome of tumor cells, possibly making them more immunogenic and thus susceptible to immune targeting.

Methods

We characterized the effects of BET bromodomain inhibition using JQ1 on PD-L1 and HLA-ABC expression in two human prostate cell lines, DU145 and PC3. RNA-Seq was performed to assess changes on a genome-wide level. A cytotoxic T cell killing assay was performed in MC38-OVA cells treated with JQ1 to demonstrate increased immunogenicity. In vivo experiments in the Myc-Cap model were conducted to show the effects of JQ1 administration in concert with anti-CTLA-4 checkpoint blockade.

Results

Here, we show that targeti

SUBMITTER: Mao W 

PROVIDER: S-EPMC6814994 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature