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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Launonen, I-M; Lyytikäinen, N; Casado, J; Anttila, EA; Szabó, A; Haltia, U-M; Jacobson, CA; Lin, JR; Maliga, Z; Howitt, BE; Strickland, KC; Santagata, S; Elias, K; D'Andrea, AD; Konstantinopoulos, PA; Sorger, PK; Färkkilä, A

Published Date

  • February 11, 2022

Published In

Volume / Issue

  • 13 / 1

Start / End Page

  • 835 -

PubMed ID

  • 35149709

Pubmed Central ID

  • PMC8837628

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-022-28389-3

Language

  • eng

Conference Location

  • England