Breast tumor microenvironment structures are associated with genomic features and clinical outcome.
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Authors
Bardwell, Helen
Zanotelli, Vito RT
Rakha, Emad
Publication Date
2022-04-18Journal Title
Nat Genet
ISSN
1061-4036
Publisher
Springer Science and Business Media LLC
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Danenberg, E., Bardwell, H., Zanotelli, V. R., Provenzano, E., Chin, S., Rueda Palacio, O., Green, A., et al. (2022). Breast tumor microenvironment structures are associated with genomic features and clinical outcome.. Nat Genet https://doi.org/10.1038/s41588-022-01041-y
Abstract
The functions of the tumor microenvironment (TME) are orchestrated by precise spatial organization of specialized 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 multitiered spatial analysis of 693 breast tumors linked to genomic and clinical data. We identified ten 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-receptor-positive disease. The multicellular structures revealed here link conserved spatial organization to local TME function and could improve patient stratification.
Sponsorship
Cancer Research UK (C14303/A17197)
Cancer Research UK (25815)
Cancer Research UK (C9545/A29580_do not transfer)
European Research Council (694620)
Cancer Research UK (A27657)
National Institute for Health Research (NIHRDH-IS-BRC-1215-20014)
Identifiers
External DOI: https://doi.org/10.1038/s41588-022-01041-y
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335642
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