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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / classification*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Computer Simulation
  • Epithelial-Mesenchymal Transition
  • Female
  • Genes, Neoplasm
  • Genetic Heterogeneity
  • Humans
  • Logistic Models
  • Neoadjuvant Therapy
  • Neoplasm Recurrence, Local / pathology
  • Phenotype
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors
  • Tumor Microenvironment*