Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer

被引：0
作者：
I.-M. Launonen
N. Lyytikäinen
J. Casado
E. A. Anttila
A. Szabó
U.-M. Haltia
C. A. Jacobson
J. R. Lin
Z. Maliga
B. E. Howitt
K. C. Strickland
S. Santagata
K. Elias
A. D. D’Andrea
P. A. Konstantinopoulos
P. K. Sorger
A. Färkkilä
机构：
[1] University of Helsinki,Research Program in Systems Oncology
[2] Helsinki University Hospital,Department of Obstetrics and Gynecology
[3] Harvard Medical School,Laboratory of Systems Pharmacology
[4] Stanford University School of Medicine,Department of Pathology
[5] Duke University Medical Center,Department of Pathology
[6] Brigham and Women’s Hospital,Department of Pathology
[7] Brigham and Women’s Hospital,Department of Obstetrics and Gynecology and Reproductive Biology
[8] Harvard Medical School,Dana
[9] Harvard Medical School,Farber Cancer Institute, Brigham and Women’s Hospital
[10] iCAN Digital Precision Cancer Medicine Flagship,Ludwig Center for Cancer Research at Harvard
来源：
Nature Communications | / 13卷
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摘要：
The majority of high-grade serous ovarian cancers (HGSCs) are deficient in homologous recombination (HR) DNA repair, most commonly due to mutations or hypermethylation of the BRCA1/2 genes. We aimed to discover how BRCA1/2 mutations shape the cellular phenotypes and spatial interactions of the tumor microenvironment. Using a highly multiplex immunofluorescence and image analysis we generate spatial proteomic data for 21 markers in 124,623 single cells from 112 tumor cores originating from 31 tumors with BRCA1/2 mutation (BRCA1/2mut), and from 13 tumors without alterations in HR genes. We identify a phenotypically distinct tumor microenvironment in the BRCA1/2mut tumors with evidence of increased immunosurveillance. Importantly, we report a prognostic role of a proliferative tumor-cell subpopulation, which associates with enhanced spatial tumor-immune interactions by CD8+ and CD4 + T-cells in the BRCA1/2mut tumors. The single-cell spatial landscapes indicate distinct patterns of spatial immunosurveillance with the potential to improve immunotherapeutic strategies and patient stratification in HGSC.
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