Macrophages in Tumor Microenvironments and the Progression of Tumors

Figure 1

Classically and alternatively activated macrophages. Classically polarized macrophages are activated by LPS, IFN-γ, or TNF-α. Alternatively polarized macrophages can be further divided into M2a, M2b, and M2c macrophages. IL-4 and IL-13 always activate macrophages to be M2a macrophages. The main difference between M1 and M2a macrophages is in their metabolism of L-arginine. In M1 macrophages, L-arginine is metabolized into L-citrulline and NO by NOS2, while in M2a macrophages, it is metabolized into polyamine and urea by arginase 1. M2b macrophages are activated by immune complexes, TLRs, or IL-1ra. Finally, M2c macrophages are polarized by IL-10. All of the phenotypes express a series of different cytokines, chemokines, and receptors.