Breast tumour microenvironment structures are associated with genomic features and clinical outcome

Abstract

The functions of the tumour microenvironment (TME) are orchestrated by precise spatial organisation of specialised cells, yet little is known about the multicellular structures that form within the TME. Here, we systematically mapped TME structures in situ using imaging mass cytometry and multi-tiered spatial analysis of 693 breast tumours linked to genomic and clinical data. We identified 10 recurrent TME structures that varied by vascular content, stromal quiescence versus activation, and leukocyte composition. These TME structures had distinct enrichment patterns among breast cancer subtypes, and some were associated with genomic profiles indicative of immune escape. Regulatory and dysfunctional T cells co-occurred in large ‘suppressed expansion’ structures. These structures were characterized by high cellular diversity, proliferating cells, and enrichment for BRCA1 and CASP8 mutations, and predicted poor outcome in estrogen-positive (ER)-positive disease. The multicellular structures revealed here link conserved spatial organisation to local TME function and could improve patient stratification.