TAMing Gliomas

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Science  18 Oct 2013:
Vol. 342, Issue 6156, pp. 290
DOI: 10.1126/science.342.6156.290-c

Tumor-associated macrophages (TAMs) facilitate tumor growth by stimulating cancer cell proliferation, by helping cancer cells evade the immune system, and by promoting tumor angiogenesis. In human cancer patients, high levels of TAMs often correlate with poor prognosis. These cells are thus an exciting target for new cancer therapies, most of them designed to destroy TAMs. In a twist on this concept, Pyonteck et al. describe a promising therapy that works not by destroying TAMs but by “reeducating” the cells so that they lose their tumor-promoting functions and instead acquire tumor-suppressive functions. In mouse models of glioma, a brain tumor that is resistant to most therapies, the authors found that administration of a brain-penetrant inhibitor of colony-stimulating factor 1 receptor (CSF-1R), a signaling protein that regulates macrophage differentiation, resulted in tumor regression. In the setting of CSF-1R inhibition, TAM survival was promoted by cytokines secreted by the glioma cells. The inhibitor produced a characteristic gene expression signature in the mouse TAMs; in TAMs found in one subtype of human glioma, the same pattern correlated with increased patient survival.

Nat. Med. 19, 10.1038/nm.3337 (2013).

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