The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
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Danenberg, E. et al. Nature Genetics. 54: 660–669 (2022).
doi: 10.1038/s41588-022-01041-y.
Summary of the findings
The functions of the tumour microenvironment (TME) are orchestrated by precise spatial organisation of specialised cells, yet we know very little about the multicellular structures that form within the TME. 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 borrowed methods used in the analysis of social networks to discover recurrent spatially conserved orientations of immune and stromal cells (TME structures). 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 ER-positive disease. The landscape of multicellular structures revealed here links conserved spatial organisation to local TME function and holds potential for better patient stratification. All data have been deposited in the public domain, and should serve as a resource for other studies of the multicellular organisation of breast cancer.
