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)loF4/80hi and MHC-IIhiF4/80lo--similar to what was observed in other tumor models. Interestingly, only the MHC-IIloF4/80hi 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-IIloF4/80hi TAM. Conversely, STAT1 deficiency upregulates M2 gene expression in MHC-IIhiF4/80lo 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.
|Number of pages||5|
|Journal||Eur. J. Immunol.|
|Publication status||Published - 1 Aug 2014|
- Tumor-associated macrophages