Multi-omics study maps how BRCA1/2 genotype shapes the immune microenvironment in high-grade serous ovarian cancer

A multi-omics analysis published in PLOS Genetics by Jing Qian, Rania Bassiouni, and colleagues at institutions including the Keck School of Medicine at the University of Southern California and the Karolinska Institute has characterised intratumoral heterogeneity and tumour immune microenvironment (TIME) composition across high-grade serous ovarian cancers (HGSOC) stratified by BRCA1/2 mutation status.

The team integrated whole-exome sequencing, total RNA sequencing, and spatial profiling approaches across a cohort of HGSOC samples. BRCA1 and BRCA2 germline and somatic mutations are established drivers of HGSOC and are associated with improved responses to platinum-based chemotherapy and PARP inhibitors. However, the mechanisms by which BRCA genotype influences the immunological composition of the tumour microenvironment have remained incompletely characterised.

The study identified distinct immunological patterns across clinico-genomic subgroups, including differences in immune cell infiltration and signalling, that may help explain observed differences in therapeutic response. The authors describe heterogeneous tissue architectures within tumours that appear to influence which immune populations are present and active. The findings are relevant to ongoing efforts to understand which HGSOC patients may benefit from immunotherapy combinations alongside standard-of-care approaches, though the authors note that further validation in larger independent cohorts will be needed.