TY - JOUR
T1 - Immune microenvironment composition in high-grade serous ovarian cancers based on BRCA mutational status
AU - Corvigno, Sara
AU - Burks, Jared K.
AU - Hu, Wei
AU - Zhong, Yanping
AU - Jennings, Nicholas B.
AU - Fleming, Nicole D.
AU - Westin, Shannon N.
AU - Fellman, Bryan
AU - Liu, Jinsong
AU - Sood, Anil K.
N1 - Funding Information:
This research was supported in part by the National Institutes of Health through MD Anderson's Cancer Center Support Grant (P30 CA016672; Flow Cytometry and Cellular Imaging Core Facility and Biostatistics Resource Group), the MD Anderson Ovarian Cancer SPORE (P50 CA217685), and grants R35 CA209904 and U01 CA213759; by the American Cancer Society; and by the Frank McGraw Memorial Chair in Cancer Research.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - BRCA
KW - Fibroblasts
KW - Immune cells
KW - Lymphocytes
KW - Multiple staining
KW - Serous ovarian cancer
KW - Tumor microenvironment
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U2 - 10.1007/s00432-021-03778-1
DO - 10.1007/s00432-021-03778-1
M3 - Article
C2 - 34476576
AN - SCOPUS:85114086344
SN - 0171-5216
VL - 147
SP - 3545
EP - 3555
JO - Journal of cancer research and clinical oncology
JF - Journal of cancer research and clinical oncology
IS - 12
ER -