Macrophages are capable of both inhibiting and promoting the growth and spread of cancers, depending on their activation state. Classically activated Ml macrophages, discussed in Chapter 10, display various anti-tumor functions. These cells can kill many tumor cells more efficiently than they can kill normal cells. How macrophages are activated by tumors is not known. Possible mechanisms include direct recognition of some surface antigens of tumor cells and activation of macrophages by IFN-y produced by tumor-specific T cells. Ml macrophages can kill tumor cells by several mechanisms, probably the same as the mechanisms of macrophage killing of infectious organisms. These include the release of lysosomal enzymes, reactive oxygen species, and nitric oxide. Ml macrophages also produce the cytokine tumor necrosis factor (TNF), which was first characterized, as its name implies, as an agent that can kill tumors. We now know it does so mainly by inducing thrombosis in tumor blood vessels. In contrast, M2 macrophages may contribute to tumor progression. These cells secrete vascular endothelial growth factor (VEGF), transforming growth factor-P (TGF-P), and other soluble factors that promote tumor angiogenesis. The role of these cells and other components of the host response in enhancing tumor growth is discussed at the end of the chapter.
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