Dynamic change of immune microenvironment in ovarian cancer following neoadjuvant chemotherapy [scRNA-seq]

Initial surgery and platinum-based chemotherapy is extensively applied to ovarian cancer. Although the majority of patients were sensitive, most relapse at later stage, highlighting the urgent need to understand the tumor microenvironment in ovarian cancer following NACT (neoadjuvant chemotherapy). Through analyzing the published scRNA-seq on human high-grade serous ovarian cancer and performing several in vitro and in vivo experiments, we found prostaglandins-mediated immunosuppressive microenvironment formation is a critical contributor to chemotherapy-resistant upon cisplatin treatment. In mechanisms, cisplatin-treated ovarian cancer cells induce the formation of MDSCs, which passivates the cytotoxicity of CD8+T cell. Moreover, we also carried out scRNA-seq on mice ovarian cancer intraperitoneal injection model to confirm our findings. Notably, Collaborative application of cisplatin and prostaglandins-specific inhibition boosts the cytotoxicity of CD8+T cell and greatly improves the effective rate compared to cisplatin monotherapy.