Single-cell Tumor-immune Microenvironment of BRCA1/2 Mutated High-grade Serous Ovarian Cancer

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Feb 12

PMID 35149709

Authors

I-M Launonen

N Lyytikainen

J Casado

E A Anttila

A Szabo

U-M Haltia

C A Jacobson

J R Lin

Z Maliga

B E Howitt

K C Strickland

S Santagata

K Elias

A D DAndrea

P A Konstantinopoulos

P K Sorger

A Farkkila

Affiliations

Soon will be listed here.

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.

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