Tam

Tumor-associated (M2-)macrophages, also called TAM, are Th2-associated, alternatively activated M2 macrophages. They are phenotypically associated with M2 macrophages and are formed in a tumor milieu in the presence of IL-4 and IL-10 and M-CSF, the macrophage colony stimulating factor, and are characterized by a marked expression of CD163 and CD206.

Tumor-associated macrophages are important components of the tumor microenvironment and represent a large proportion of the immune cells infiltrating the tumor (Hagemann S 2015). They have complex functions and can have pro- or antitumour effects depending on their activation state (classical or alternative) (Ma J L et al. 2010; Partecke LI et al. 2013).

Most TAM are derived from peripheral monocytes that migrate into the neoplastic tissue by chemotactic cytokines. The most important trend-setting cytokines of human tumors are monocyte chemotactic protein-1 (MCP-1/CCL-2), macrophage colony stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF). MCP-1 is a chemokine that regulates angiogenesis and causes tumor growth to progress. Furthermore, a local IL-4 induced macrophage proliferation of resident macrophages is also suspected (Mantovani AG et al. 2011).

The tumor cells usually induce an alternative activation of TAMs to M2 macrophages by secreting IL-10 and simultaneously blocking maturation into dendritic cells (Mantovani AG et al. 2011). IL-10 activates Th2 cells, which in turn enhance the alternative activation of TAMs by secreting transforming growth factor beta (TGF-β), IL-4, IL-10 and IL-13. IL-4, IL-10, IL-13 and TGF-β are also secreted into the micromilieu by tumor cells as anti-inflammatory mediators and inhibit the ability of macrophages to lyse tumor tissue (Lewis CE et al. 2006).

As a result, malignant cells are able to suppress the immune defence by TAMs and cause immune suppression (Lewis CE et al. 2006). M2 macrophages also produce large amounts of IL-10 and TGF-β. Thus, the immunosuppressive microenvironment in the tumour is also maintained by the macrophages themselves.

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