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

Autor: Theodore S. Kapellos, Cheei-Sing Hau, Thomas Ulas, Lea Seep, Kathrin Klee, Sander Tuit, Karin E. de Visser, Joachim L. Schultze, Marie Oestreich, Camilla Salvagno
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Transcription
Genetic
Carcinogenesis
pathology [Carcinogenesis]
genetics [Transcriptome]
clinical outcome prediction
co-expression network analysis
Transcriptome
tumor-associated macrophage
0302 clinical medicine
genetics [Carcinogenesis]
pathology [Mammary Neoplasms
Animal]
skin and connective tissue diseases
innate immunity
lcsh:QH301-705.5
Mice
Inbred BALB C
genetics [Breast Neoplasms]
Prognosis
3. Good health
Gene Expression Regulation
Neoplastic
Phenotype
Treatment Outcome
Invasive lobular carcinoma
Female
hormones
hormone substitutes
and hormone antagonists
Genetically modified mouse
mouse model
Breast Neoplasms
Mammary Neoplasms
Animal
Mice
Transgenic
Tumor-associated macrophage
Biology
pathology [Breast Neoplasms]
metabolism [RNA
Messenger]
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
genetics [RNA
Messenger]
Breast cancer
Immune system
breast cancer
stomatognathic system
genetics [Mammary Neoplasms
Animal]
invasive lobular carcinoma
medicine
Animals
Humans
human
RNA
Messenger
ddc:610
Innate immune system
Macrophages
Gene Expression Profiling
Cancer
medicine.disease
Survival Analysis
Disease Models
Animal
030104 developmental biology
lcsh:Biology (General)
Cancer research
metabolism [Macrophages]
030217 neurology & neurosurgery
Zdroj: Cell reports 29(5), 1221-1235.e5 (2019). doi:10.1016/j.celrep.2019.09.067
Cell Reports, Vol 29, Iss 5, Pp 1221-1235.e5 (2019)
Cell Reports
DOI: 10.1016/j.celrep.2019.09.067
Popis: Summary 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.
Graphical Abstract
Highlights • Murine TAM signatures prognosticate outcomes in corresponding cancer patients • TAM signatures are robust when they are compared with healthy tissue macrophages • TAM transcriptome is dictated by tissue and tumor subtype-related signals • Murine TAM signatures can be translated only when a suitable model is chosen
Tuit et al. show that TAM transcriptomes in murine models of breast cancer are governed mainly by tissue and tumor subtype-specific signals. Clinical translation of murine signatures can be achieved when human and mouse breast tumor subtypes are matched and only upon proper comparison of TAMs with healthy tissue macrophages.
Databáze: OpenAIRE
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