Sequential azacitidine and carboplatin can prime high-grade serous ovarian cancer to respond to checkpoint inhibitor immunotherapy.

Platinum chemoresistance results in disease recurrence in patients with high-grade serous ovarian cancer (HGSOC). Recent advances in the treatment of solid tumours using checkpoint inhibitor immunotherapy has not benefited platinum-resistant HGSOC. Epigenetic silencing of genes involved in triggering cell death and apoptosis in HGSOC is known to occur via hypermethylation during development of platinum resistance. DNA methyltransferase (DNMT) inhibitors block methylation from occurring and allow silenced genes to be expressed. In ovarian cancer, DNMT inhibitors alter the epigenome and transcriptome of the tumours, which primarily affected expression of immune reactivation pathways. We aimed to determine the epigenome and transcriptome response to sequential treatment of HGSOC cells with DNMTi followed by standard-of-care carboplatin. Overall design: High-grade serous ovarian cancer cell lines confirmed by genomic and proteomic profiling to be HGSOC cell lines were treated with 0.5 µM azacitidine every 24hr for 72hr, followed by 20µM carboplatin for 48hr. RNA was extracted from these cell lines after sequential azacitidine and carboplatin treatment.