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dc.contributor.author
Danenberg, Esther
dc.contributor.author
Bardwell, Helen
dc.contributor.author
Zanotelli, Vito R.T.
dc.contributor.author
Provenzano, Elena
dc.contributor.author
Chin, Suet-Feung
dc.contributor.author
Rueda, Oscar M.
dc.contributor.author
Green, Andrew
dc.contributor.author
Rakha, Emad
dc.contributor.author
Aparicio, Samuel
dc.contributor.author
Ellis, Ian O.
dc.contributor.author
Bodenmiller, Bernd
dc.contributor.author
Caldas, Carlos
dc.contributor.author
Ali, H. Raza
dc.date.accessioned
2022-05-20T08:51:04Z
dc.date.available
2022-04-29T03:20:25Z
dc.date.available
2022-04-29T11:40:28Z
dc.date.available
2022-05-20T08:51:04Z
dc.date.issued
2022-05
dc.identifier.issn
1061-4036
dc.identifier.issn
1546-1718
dc.identifier.other
10.1038/s41588-022-01041-y
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/544285
dc.identifier.doi
10.3929/ethz-b-000544285
dc.description.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.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Breast tumor microenvironment structures are associated with genomic features and clinical outcome
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2022-04-18
ethz.journal.title
Nature Genetics
ethz.journal.volume
54
en_US
ethz.journal.issue
5
en_US
ethz.journal.abbreviated
Nat Genet
ethz.pages.start
660
en_US
ethz.pages.end
669
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
New York, NY
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::09735 - Bodenmiller, Bernd / Bodenmiller, Bernd
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::09735 - Bodenmiller, Bernd / Bodenmiller, Bernd
ethz.date.deposited
2022-04-29T03:21:11Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2022-05-20T08:51:12Z
ethz.rosetta.lastUpdated
2024-02-02T17:17:12Z
ethz.rosetta.versionExported
true
ethz.COinS
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