# Dynamic changes of the immune microenvironment in ovarian cancer following neoadjuvant chemotherapy

## TL;DR

This paper explores how ovarian cancer becomes resistant to chemotherapy and suggests that targeting prostaglandins could improve treatment outcomes.

## Contribution

The study identifies prostaglandin-mediated immunosuppression as a novel mechanism of chemotherapy resistance in ovarian cancer.

## Key findings

- Cisplatin treatment promotes the formation of myeloid-derived suppressor cells, which inhibit CD8+T cell activity.
- Combining cisplatin with a prostaglandin inhibitor restores T cell function and improves therapeutic efficacy.
- Prostaglandins play a critical role in creating an immunosuppressive environment in ovarian cancer.

## Abstract

Standard treatment for advanced ovarian cancer involves initial surgery followed by platinum-based chemotherapy. Although most patients are sensitive, most relapses occur at a later stage, highlighting the urgent need to understand the tumour microenvironment following neoadjuvant chemotherapy (NACT). To explore the mechanisms underlying chemotherapy resistance, we analysed published single-cell RNA sequencing (scRNA-seq) data from patients with high-grade serous ovarian cancer and performed several in vitro and in vivo experiments to investigate the role of prostaglandins in immunosuppressive microenvironment formation. Prostaglandin-mediated immunosuppressive microenvironment formation was a critical contributor to chemotherapy resistance following cisplatin treatment. Mechanistically, cisplatin-treated ovarian cancer cells induced the formation of myeloid-derived suppressor cells (MDSCs), which inhibited the cytotoxicity of CD8+T cells. Combination therapy with cisplatin and a prostaglandin-specific inhibitor restored CD8+T cell function and significantly improved the therapeutic efficacy compared with cisplatin monotherapy. Targeting prostaglandins may be a promising therapeutic strategy for overcoming chemotherapy resistance in ovarian cancer.