A Single-Cell Atlas of the Tumor and Immune Ecosystem of Human Breast Cancer.
- Wagner J Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland; Molecular Life Sciences Ph.D. Program, Life Science Zurich Graduate School, ETH Zurich and University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
- Rapsomaniki MA IBM Research Zurich, Saeumerstrasse 4, 8803 Rueschlikon, Switzerland.
- Chevrier S Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
- Anzeneder T Patients' Tumor Bank of Hope (PATH) Biobank, PO 750729, 81337 Munich, Germany.
- Langwieder C Institute of Pathology at Josefshaus, Amalienstrasse 21, 44137 Dortmund, Germany.
- Dykgers A Institute of Pathology at Josefshaus, Amalienstrasse 21, 44137 Dortmund, Germany.
- Rees M Institute of Pathology at Josefshaus, Amalienstrasse 21, 44137 Dortmund, Germany.
- Ramaswamy A Institute of Pathology, University Hospital Giessen and Marburg, Baldingerstrasse, 35043 Marburg, Germany.
- Muenst S Institute of Pathology, University Hospital Basel and University of Basel, Schoenbeinstrasse 40, 4031 Basel, Switzerland.
- Soysal SD Clarunis, University Hospital Basel and University of Basel, Spitalstrasse 21, 4031 Basel, Switzerland; Breast Cancer Center, University Hospital Basel and University of Basel, Spitalstrasse 21, 4031 Basel, Switzerland.
- Jacobs A Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
- Windhager J Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland; Systems Biology Ph.D. Program, Life Science Zurich Graduate School, ETH Zurich and University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
- Silina K Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
- van den Broek M Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
- Dedes KJ Breast Cancer Center, University Hospital Zurich, Frauenklinikstrasse 10, 8091 Zurich, Switzerland.
- Rodríguez Martínez M IBM Research Zurich, Saeumerstrasse 4, 8803 Rueschlikon, Switzerland.
- Weber WP Breast Cancer Center, University Hospital Basel and University of Basel, Spitalstrasse 21, 4031 Basel, Switzerland; Department of Surgery, University Hospital Basel and University of Basel, Spitalstrasse 21, 4031 Basel, Switzerland.
- Bodenmiller B Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address: bernd.bodenmiller@imls.uzh.ch.
- 2019-04-16
Published in:
- Cell. - 2019
T cell
breast cancer
immunosuppression
macrophage
mass cytometry
single-cell analysis
tumor ecosystem
tumor heterogeneity
B7-H1 Antigen
Breast Neoplasms
Cell Line, Tumor
Disease-Free Survival
Female
Humans
Immune Tolerance
Lymphocytes, Tumor-Infiltrating
Macrophages
Neoplasm Proteins
Survival Rate
Tumor Microenvironment
English
Breast cancer is a heterogeneous disease. Tumor cells and associated healthy cells form ecosystems that determine disease progression and response to therapy. To characterize features of breast cancer ecosystems and their associations with clinical data, we analyzed 144 human breast tumor and 50 non-tumor tissue samples using mass cytometry. The expression of 73 proteins in 26 million cells was evaluated using tumor and immune cell-centric antibody panels. Tumors displayed individuality in tumor cell composition, including phenotypic abnormalities and phenotype dominance. Relationship analyses between tumor and immune cells revealed characteristics of ecosystems related to immunosuppression and poor prognosis. High frequencies of PD-L1+ tumor-associated macrophages and exhausted T cells were found in high-grade ER+ and ER- tumors. This large-scale, single-cell atlas deepens our understanding of breast tumor ecosystems and suggests that ecosystem-based patient classification will facilitate identification of individuals for precision medicine approaches targeting the tumor and its immunoenvironment.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1016/j.cell.2019.03.005
- PMID 30982598
- Persistent URL
- https://folia.unifr.ch/global/documents/136458
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