Immunological Approaches for ARID1A-Mutated Ovarian Cancer
Abstract
ARID1A encodes a subunit of the SWI/SNF chromatin-remodeling complex and functions as a tumor suppressor. Notably, inactivating mutations in ARID1A occur frequently in ovarian clear cell carcinomas (OCCC; >50%) and ovarian endometrioid carcinomas (OEC; >30%). There is an unmet need for effective treatment modalities for ARID1A-mutated ovarian cancers. Our preliminary data show that ARID1A mutation sensitizes ovarian cancer to anti-PD-L1 treatment. Our recent studies also show that ARID1A-mutated ovarian cancer depends on HDAC6 activity. Although most translational studies on HDAC6 inhibitors have focused on their effects on tumor cells, emerging evidence suggests that HDAC6 inhibitors have immunomodulatory effects on various immune cellular subsets. Indeed, our preliminary data suggests that the HDAC6 inhibitor ACY1215 enhances the activation of T cells and suppresses MDSCs in ARID1A-mutated OCCCs. They suggest that HDAC6 inhibitors may enhance the anti-PD-L1 therapy in ARID1A-mutated ovarian cancers. Our central hypothesis is that ARID1A-mutated ovarian cancer can be therapeutically eradicated by a combination of clinically applicable HDAC6 inhibitor and anti-PD-L1 immune checkpoint blockade.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1126902
Entities
People
- Rugang Zhang
Organizations
- Wistar Institute