HDAC6 Inhibition Synergizes with Anti-PD-L1 Therapy in ARID1A-Inactivated Ovarian Cancer.

ABSTRACT: ARID1A, encoding a subunit of the SWI/SNF complex, is the most frequently mutated epigenetic regulator in human cancers and is mutated in more than 50% of ovarian clear cell carcinomas (OCCC), a disease that currently has no effective therapy. Inhibition of histone deacetylase 6 (HDAC6) suppresses the growth of ARID1A-mutated tumors and modulates tumor immune microenvironment. Here, we show that inhibition of HDAC6 synergizes with anti-PD-L1 immune checkpoint blockade in ARID1A-inactivated ovarian cancer. ARID1A directly repressed transcription of CD274, the gene encoding PD-L1. Reduced tumor burden and improved survival were observed in ARID1A^flox/flox/PIK3CA^H1047R OCCC mice treated with the HDAC6 inhibitor ACY1215 and anti-PD-L1 immune ch

SUBMITTER: Fukumoto T 

PROVIDER: S-EPMC6825538 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature