Transcriptional Signature Derived from Murine Tumor-Associated Macrophages Correlates with Poor Outcome in Breast Cancer Patients

Cell Rep. 2019 Oct 29;29(5):1221-1235.e5. doi: 10.1016/j.celrep.2019.09.067.


Tumor-associated macrophages (TAMs) are frequently the most abundant immune cells in cancers and are associated with poor survival. Here, we generated TAM molecular signatures from K14cre;Cdh1flox/flox;Trp53flox/flox (KEP) and MMTV-NeuT (NeuT) transgenic mice that resemble human invasive lobular carcinoma (ILC) and HER2+ tumors, respectively. Determination of TAM-specific signatures requires comparison with healthy mammary tissue macrophages to avoid overestimation of gene expression differences. TAMs from the two models feature a distinct transcriptomic profile, suggesting that the cancer subtype dictates their phenotype. The KEP-derived signature reliably correlates with poor overall survival in ILC but not in triple-negative breast cancer patients, indicating that translation of murine TAM signatures to patients is cancer subtype dependent. Collectively, we show that a transgenic mouse tumor model can yield a TAM signature relevant for human breast cancer outcome prognosis and provide a generalizable strategy for determining and applying immune cell signatures provided the murine model reflects the human disease.

Keywords: breast cancer; clinical outcome prediction; co-expression network analysis; human; innate immunity; invasive lobular carcinoma; mouse model; transcriptome; tumor-associated macrophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Disease Models, Animal
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Macrophages / metabolism*
  • Mammary Neoplasms, Animal / genetics
  • Mammary Neoplasms, Animal / pathology*
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Phenotype
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Survival Analysis
  • Transcription, Genetic*
  • Transcriptome / genetics
  • Treatment Outcome


  • RNA, Messenger