Temporal and disease-site specific transcriptional and phenotypic changes in response to neoadjuvant chemotherapy in high-grade serous ovarian cancers

Abstract Neoadjuvant chemotherapy (NACT) has been known to induce genomic and transcriptomic alterations within tumours. Here, using transcriptome profiling along with histological analysis of pre and post NACT, we show temporal and disease site-specific differences (omentum, ovary and other sites) in high grade serous ovarian cancer (HGSOC) and their association with progression free and overall survival. We observed a significant reduction in genome instability signature score following NACT irrespective of disease site, which correlated with homologous recombination repair (HRR) function measured by RAD51 foci formation. However, increase in immuno-oncology and inflammation signatures was only observed in the omentum and not in the ovary post-NACT. DNA damage immune response (DDIR) along with HRR function were strongly associated with CD8+ T-cell infiltration within tumours. Our study provides transcriptomic and phenotypic data highlighting the heterogeneity in HGSOCs during the course of treatment and indicating how the tumour evolves in response to NACT.