Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer.
IF: 17.694
Cited by: 15


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.


Spatial Proteomics

MeSH terms

BRCA1 Protein
BRCA2 Protein
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Carcinoma, Ovarian Epithelial
Cystadenocarcinoma, Serous
Genes, BRCA1
Genes, BRCA2
Homologous Recombination
Ovarian Neoplasms
Tumor Microenvironment


Launonen, I-M
Lyytikäinen, N
Casado, J
Anttila, E A
Szabó, A
Haltia, U-M
Jacobson, C A
Lin, J R
Maliga, Z
Howitt, B E
Strickland, K C
Santagata, S
Elias, K
D'Andrea, A D
Konstantinopoulos, P A
Sorger, P K
Färkkilä, A

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