Journal
CELL REPORTS
Volume 29, Issue 5, Pages 1221-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2019.09.067
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Funding
- People Programme (Marie Sklodowska-Curie Actions) of the European Union [317445]
- Deutsche Forschungsgemeinschaft (DFG
- German Research Foundation) under Germany's Excellence Strategy [EXC2151 - 390873048]
- European Union [733100]
- Dutch Cancer Society [NKI10623]
- European Research Council (ERC) [INFLAMET 615300]
- NWO [VICI 91819616]
- Helmholtz Association
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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;Cdh1(flox/flox);Trp53(flox/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.
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