Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77054, USA.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Cancer Res Clin Oncol. 2021 Dec;147(12):3545-3555. doi: 10.1007/s00432-021-03778-1. Epub 2021 Sep 2.
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.
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.
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-L1CD8 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 FAPPD-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).
This study reveals substantial differences between the immune microenvironment composition of germline BRCA-mutated and BRCA wild-type HGSC.
需要深入分析卵巢癌的肿瘤微环境。本研究旨在阐明有无 BRCA1 和 BRCA2 突变的高级别浆液性卵巢癌（HGSC）的免疫微环境结构。
选择了一组具有已知种系 BRCA1 和 BRCA2 状态的高度注释的 HGSC 患者队列，并使用旨在检测整个肿瘤区域以及上皮、基质和血管周围区域等特定区域中的淋巴细胞、巨噬细胞和成纤维细胞的多重染色技术分析预处理肿瘤组织标本。
BRCA1 或 BRCA2 突变型肿瘤的免疫微环境更具免疫原性，其 CD8 和 PD-L1 细胞丰度高于 BRCA1 和 BRCA2 野生型肿瘤。高数量的 PD-L1 和 PD-L1CD8 细胞与无事件生存相关（风险比 [HR]：0.41，95%CI 0.21-0.79，p=0.008 和 HR 0.49，95%CI 0.26-0.91，p=0.025），上皮 PD-L1 和 FAPPD-L1 细胞（HR 0.52，95%CI 0.28-0.96，p=0.037 和 HR 0.27，95%CI 0.08-0.87，p=0.029）和 CD8 细胞（HR 0.51，95%CI 0.28-0.93，p=0.027）数量也很高。
本研究揭示了种系 BRCA 突变和 BRCA 野生型 HGSC 免疫微环境组成之间存在显著差异。
