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Nat Commun. 2019 Dec 3;10(1):5499. doi: 10.1038/s41467-019-13329-5.

An independent poor-prognosis subtype of breast cancer defined by a distinct tumor immune microenvironment.

Author information

1
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
2
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
3
Department of Oncology, Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway.
4
Department of Pathology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway.
5
Division of Oncology and Pathology, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Scheelegatan 2, Medicon Village, 22185, Lund, Sweden.
6
Department of Biostatistics, Oslo Centre for Biostatistics and Epidemiology, University of Oslo and Research Support Services, Oslo University Hospital, Oslo, Norway.
7
Department of Research, Vestre Viken Hospital Trust, Drammen, Norway.
8
Centre for Cancer Biomarkers CCBIO, Bergen, Norway.
9
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
10
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Vessela.N.Kristensen@rr-research.no.
11
Centre for Cancer Biomarkers CCBIO, Bergen, Norway. Vessela.N.Kristensen@rr-research.no.
12
Department of Clinical Molecular Biology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway. Vessela.N.Kristensen@rr-research.no.

Abstract

How mixtures of immune cells associate with cancer cell phenotype and affect pathogenesis is still unclear. In 15 breast cancer gene expression datasets, we invariably identify three clusters of patients with gradual levels of immune infiltration. The intermediate immune infiltration cluster (Cluster B) is associated with a worse prognosis independently of known clinicopathological features. Furthermore, immune clusters are associated with response to neoadjuvant chemotherapy. In silico dissection of the immune contexture of the clusters identified Cluster A as immune cold, Cluster C as immune hot while Cluster B has a pro-tumorigenic immune infiltration. Through phenotypical analysis, we find epithelial mesenchymal transition and proliferation associated with the immune clusters and mutually exclusive in breast cancers. Here, we describe immune clusters which improve the prognostic accuracy of immune contexture in breast cancer. Our discovery of a novel independent prognostic factor in breast cancer highlights a correlation between tumor phenotype and immune contexture.

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