Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35149709.
- Also identified by DOI 10.1038/s41467-022-28389-3 and PMC identifier 8837628.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- BRCA1 Protein
- BRCA2 Protein
- Carcinoma, Ovarian Epithelial
- Cystadenocarcinoma, Serous
- Ovarian Neoplasms
- Tumor Microenvironment