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

Xavier Tekpli, Tonje Lien, Andreas Hagen Røssevold, Daniel Nebdal, Elin Borgen, Hege Oma Ohnstad, Jon Amund Kyte, Johan Vallon-Christersson, Marie Fongaard, Eldri Undlien Due, Lisa Gregusson Svartdal, My Anh Tu Sveli, Øystein Garred, Arnoldo Frigessi, Kristine Kleivi Sahlberg, Therese Sørlie, Hege G. Russnes, Bjørn Naume and Vessela N. Kristensen ()
Additional contact information
Xavier Tekpli: Institute for Cancer Research, Oslo University Hospital
Tonje Lien: Institute for Cancer Research, Oslo University Hospital
Andreas Hagen Røssevold: Institute for Cancer Research, Oslo University Hospital
Daniel Nebdal: Institute for Cancer Research, Oslo University Hospital
Elin Borgen: Oslo University Hospital
Hege Oma Ohnstad: Oslo University Hospital
Jon Amund Kyte: Institute for Cancer Research, Oslo University Hospital
Johan Vallon-Christersson: Lund University
Marie Fongaard: Institute for Cancer Research, Oslo University Hospital
Eldri Undlien Due: Institute for Cancer Research, Oslo University Hospital
Lisa Gregusson Svartdal: Oslo University Hospital
My Anh Tu Sveli: Oslo University Hospital
Øystein Garred: Oslo University Hospital
Arnoldo Frigessi: Oslo Centre for Biostatistics and Epidemiology, University of Oslo and Research Support Services, Oslo University Hospital
Kristine Kleivi Sahlberg: Institute for Cancer Research, Oslo University Hospital
Therese Sørlie: Institute for Cancer Research, Oslo University Hospital
Hege G. Russnes: Institute for Cancer Research, Oslo University Hospital
Bjørn Naume: Oslo University Hospital
Vessela N. Kristensen: Institute for Cancer Research, Oslo University Hospital

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13329-5

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