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nature portfolio privacy policy deletion-derived tumour-specific neoantigens advertising paraffin-embedded cancer tissue social media scientific advisory board author information authors reprints gene-expression-based retrospective study european research council arc-hyperbolic-sine transformed log-transformed pan-cytokeratin counts agarose-coated glass slide european genome-phenome archive medical research council high-dimensional imaging revealed receiver-operating characteristic statistics cancer research uk multidimensional nature thermo scientific original author cox proportional-hazards models clustering solutions contractile matrix-producing fibroblasts31 cellular flice-inhibitory protein high-resolution sequencing data intra-tumoral niche maintains driver copy-number aberrations21 data-driven phenotypic dissection organ-specific immune responses driver copy-number alterations21 er-positive breast cancer41 generate high-dimensional images metal-tagged secondary antibody permissions community-detection algorithm based structured tumor-immune microenvironment estrogen-receptor-positive disease nature nature 577 nature 578 nature 486 nature 567 nature 406 nature 576 nature 596 nature 597 nature 583 processed single-cell data

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         headline:Breast tumor microenvironment structures are associated with genomic features and clinical outcome
         description: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. Imaging mass cytometry profiling of 693 breast tumors identified 10 recurrent tumor microenvironment spatial structures. These structures were enriched in different molecular subtypes and can be associated with genomic profiles and outcomes.
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      url:http://orcid.org/0000-0002-6325-7861
      affiliation:
            name:University of Zurich
            address:
               name:Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland
               type:PostalAddress
            type:Organization
            name:ETH Zurich
            address:
               name:Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Carlos Caldas
      url:http://orcid.org/0000-0003-3547-1489
      affiliation:
            name:University of Cambridge
            address:
               name:CRUK Cambridge Institute, University of Cambridge, Cambridge, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:H. Raza Ali
      url:http://orcid.org/0000-0001-7587-0906
      affiliation:
            name:University of Cambridge
            address:
               name:CRUK Cambridge Institute, University of Cambridge, Cambridge, UK
               type:PostalAddress
            type:Organization
            name:University of Zurich
            address:
               name:Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland
               type:PostalAddress
            type:Organization
            name:Addenbrookes Hospital
            address:
               name:Department of Histopathology, Addenbrookes Hospital, Cambridge, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:CRUK Cambridge Institute, University of Cambridge, Cambridge, UK
      name:Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland
      name:CRUK Cambridge Institute, University of Cambridge, Cambridge, UK
      name:Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland
      name:Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland
      name:Department of Histopathology, Addenbrookes Hospital, Cambridge, UK
      name:CRUK Cambridge Institute, University of Cambridge, Cambridge, UK
      name:MRC Biostatistics Unit, University of Cambridge, Cambridge, UK
      name:Department of Pathology, University of Nottingham, Nottingham, UK
      name:Department of Pathology, University of Nottingham, Nottingham, UK
      name:British Columbia Cancer Agency, University of British Columbia, Vancouver, Canada
      name:Department of Pathology, University of Nottingham, Nottingham, UK
      name:Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland
      name:Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland
      name:CRUK Cambridge Institute, University of Cambridge, Cambridge, UK
      name:CRUK Cambridge Institute, University of Cambridge, Cambridge, UK
      name:Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland
      name:Department of Histopathology, Addenbrookes Hospital, Cambridge, UK

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