title: STAT of the union: dynamics of distinct tumor-associated macrophage subsets governed by STAT1.
abstract: The tumor stroma has long been ignored as therapeutic target, but it has become clear that several stromal cell types play a nonredundant role during tumor progression. In particular, macrophages possess the capacity to stimulate tumor growth and metastasis via multiple mechanisms. In this issue of the European Journal of Immunology, a study by Tymoszuk et al. Eur. J. Immunol. 2014. 44: 2247-2262 demonstrates that both monocyte recruitment and local macrophage proliferation determines the tumor-associated macrophage (TAM) pool size in HER2/Neu-driven mammary carcinomas. These tumors contain two main TAM subsets--MHC class II (MHC-II)(lo) F4/80(hi) and MHC-II(hi) F4/80(lo)--similar to what was observed in other tumor models. Interestingly, only the MHC-II(lo) F4/80(hi) subset is largely absent in a STAT1-deficient background. STAT1 induces the expression of CSF-1, which in turn drives TAM proliferation and possibly also the M2 gene signature of MHC-II(lo) F4/80(hi) TAM. Conversely, STAT1 deficiency upregulates M2 gene expression in MHC-II(hi) F4/80(lo) TAM, demonstrating that both TAM subsets are differentially regulated, probably as a consequence of their distinct intratumoral localization. In this Commentary, we place these findings in the context of current knowledge and propose new avenues for future research.
authors: Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Eva
authors: E
authors: Van Overmeire
authors: Damya
authors: D
authors: Laoui
authors: Jiri
authors: J
authors: Keirsse
authors: Stefano
authors: S
authors: Bonelli
authors: Qods
authors: Q
authors: Lahmar
authors: Jo A
authors: JA
authors: Van Ginderachter
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D005802:Genes, MHC Class II / Q000276:immunology; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000276:immunology / Q000378:metabolism*
chemical_list: D016173:Macrophage Colony-Stimulating Factor; D018719:Erb-b2 Receptor Tyrosine Kinases; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human
keywords: CSF-1; Ontogeny; Stat1; Tumor-associated macrophages