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

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 and A. Färkkilä ()
Additional contact information
I.-M. Launonen: University of Helsinki
N. Lyytikäinen: University of Helsinki
J. Casado: University of Helsinki
E. A. Anttila: University of Helsinki
A. Szabó: University of Helsinki
U.-M. Haltia: University of Helsinki
C. A. Jacobson: Harvard Medical School
J. R. Lin: Harvard Medical School
Z. Maliga: Harvard Medical School
B. E. Howitt: Stanford University School of Medicine
K. C. Strickland: Duke University Medical Center
S. Santagata: Harvard Medical School
K. Elias: Brigham and Women’s Hospital
A. D. D’Andrea: Harvard Medical School
P. A. Konstantinopoulos: Harvard Medical School
P. K. Sorger: Harvard Medical School
A. Färkkilä: University of Helsinki

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-28389-3

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