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

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.

Automated summary

In this study, differences between the immune microenvironment composition of germline BRCA-mutated and BRCA wild-type HGSC were substantial. Tumors with BRCA1 or BRCA2 mutations exhibited a more immunogenic microenvironment with higher levels of CD8(+) and PD-L1(+) cells compared to wild-type BRCA1 and BRCA2 tumors. High numbers of specific immune cells were associated with improved event-free survival in HGSC patients.