Tumor-associated macrophages (TAM) are very abundant in
tumors and are thought to play a major role in promoting
tumor growth. The generation of TAM is positively regulated by several
cytokines, including colony stimulating factor-1 (CSF-1) and
monocyte chemoattractant protein-1 (CCL2). However, endogenous factors that suppress the generation of TAM within
tumors have not been previously identified. An earlier study showed that endogenously produced
type I interferons (IFN) suppressed
tumor growth via their effects on hematopoietic cells rather than through direct effects on
tumor cells. Therefore, we used mouse
tumor models to investigate the effects of endogenously produced type I IFNs on the generation of TAM. We found using immunohistochemistry and flow cytometry that TAM density was significantly increased in
tumors of mice lacking the type I IFN receptor (IFN-alpha/betaR(-/-) mice) compared to wild type mice. Moreover, the increase in TAM density was associated with a significant increase in
tumor growth rate and angiogenesis. The phenotype of TAM was similar in IFN-alpha/betaR(-/-) mice and wild type mice and
tumors in both mice produced similar amounts of
CSF-1 and CCL2. However, in vitro assays indicated that low concentrations of type I IFNs significantly inhibited the generation of bone marrow macrophages in response to
CSF-1. These findings indicate that endogenously produced type I IFNs suppress the generation of TAM, which may in turn account for inhibition of
tumor growth and angiogenesis.