Neoadjuvant and adjuvant pembrolizumab for advanced high-grade serous carcinoma (NeoPembrOV): A randomized phase II GINECO clinical trial
PD-1/PD-L1 blockade did not show survival benefit in high grade ovarian carcinomas. By using paired samples from the NeoPembrOv randomized phase II trial and by combining RNA-seq and multiplexed immunofluorescence stainings, we explored the impact of NeoAdjuvant ChemoTherapy (NACT) ± Pembrolizumab (P) on the tumor environment and identified parameters correlating to response. 1) The combination therapy resulted in a significant increase of intraepithelial CD8+PD-1+ T cells that correlated to clinical benefit. 2) High CD8B/FOXP3 and high CD8B/ENTPD1 ratios were significantly associated with response to NACT+P, while KDR and VEGFR2 expression were associated with resistance. 3) Combining endothelial and monocyte signatures and the CD8B/FOXP3 ratio predicted response to NACT+P with an AUC of 0.93 (95% CI 0.84–1.00). These results indicate that targeting regulatory T cells and endothelial cells, especially VEGFR2+ endothelial cells, could overcome ovarian cancer immune resistance. Overall design: We explored the impact of NeoAdjuvant ChemoTherapy (NACT) ± Pembrolizumab (P) on the tumor environment.