Immune microenvironment composition in high-grade serous ovarian cancers based on BRCA mutational status

Abstract

Purpose: An in-depth analysis of the tumor microenvironment of ovarian cancer is needed. The purpose of this study was to elucidate the architecture of the immune microenvironment of high-grade serous ovarian cancers (HGSCs) with or without BRCA1 and BRCA2 mutations.

Methods: A cohort of highly annotated HGSC patients with known germline BRCA1 and BRCA2 status was selected, and pretreatment tumor tissue specimens were analyzed with a multiplexed staining technique aimed at detecting lymphocytes, macrophages, and fibroblasts in the whole tumor area and in specific regions including epithelium, stroma, and perivascular areas.

Results: BRCA1- or BRCA2-mutated tumors showed a more immunogenic microenvironment, characterized by a higher abundance of CD8⁺ and PD-L1⁺ cells, than did tumors with wild-type BRCA1 and BRCA2. High numbers of PD-L1⁺ and PD-L1⁺CD8⁺ cells were prognostic for event-free survival (hazard ratio [HR]: 0.41, 95% CI 0.21-0.79, p = 0.008 and HR 0.49, 95% CI 0.26-0.91, p = 0.025, respectively), as were high numbers of epithelial PD-L1⁺ and FAP⁺PD-L1⁺ cells (HR 0.52, 95% CI 0.28-0.96, p = 0.037 and HR 0.27, 95% CI 0.08-0.87, p = 0.029) and CD8⁺ cells (HR 0.51, 95% CI 0.28-0.93, p = 0.027).

Conclusions: This study reveals substantial differences between the immune microenvironment composition of germline BRCA-mutated and BRCA wild-type HGSC.

Keywords: BRCA; Fibroblasts; Immune cells; Lymphocytes; Multiple staining; Serous ovarian cancer; Tumor microenvironment.