A thorough analysis of breast tumor microenvironment structures by Imaging Mass Cytometry (IMC) showed that recurrent pattern are linked to clinical outcomes and are associated with genomic profiles indicative of immune escape. These results were recently published in Nature Genetics and could improve patient stratification.
The landscape of tumor microenvironment structures in breast cancer and its relationship to genomic features and clinical outcome were investigated by using data collected on 693 patients recruited in the METABRIC trial. This case series of breast cancer patients is the largest to have been widely characterized at the molecular level and is therefore a source of valuable information, generated by Prof. Carlos Caldas lab and collaborators at the Cancer Research UK Cambridge Institute. It is also one of the largest cohorts where the recently developed IMC technology has been successfully applied to study the spatial organization and heterogeneity of both the tumor and its microenvironment at single cell resolution. In this new study, researchers at the Cancer Research UK Cambridge Institute used IMC and identified ten recurrent tumor microenvironment structures that varied by vascular content, stromal quiescence versus activation and leukocyte composition and showed distinct associations with somatic alterations and genomic breast cancer subtypes; moreover, some patterns were associated with genomic profiles indicative of immune escape. Regulatory and dysfunctional T cells co-occurred in large ‘suppressed expansion’ structures, characterized by high cellular diversity, proliferating cells and enrichment for specific mutations; these breast tumor microenvironment structures predicted poor outcome in estrogen-receptor-positive disease. «To identify new therapeutic targets, it will be critical to understand the dynamic functional states of the tumor microenvironment: in our study, IMC revealed how the specialized cells of the breast tumor microenvironment organize in space, how this organization varies across tumors and how various structures impact clinical outcomes. This approach enables a deeper understanding of structural immunity in tumors and may help identify patients likely to respond to therapies that function by perturbing spatial organization of the tumor microenvironment», authors conclude.