Tumor-Associated Macrophages in Glioma: Friend or Foe?

Figure 1

Microglia in glioma are polarized. M1 (classically activated macrophages) and M2 (alternatively activated macrophages) differ with respect to activating signals, receptor expression, cytokine/chemokine production, and biological behavior. When mononuclear/phagocytic cells are stimulated by IFN-γ lipopolysaccharides and other microbial products, they differentiate into the M1 phenotype. Microbial products are recognized by pattern recognition receptors (PRRs) on the surface of M1, such as TLRs, and stimulate the production of pro-inflammatory cytokines as well as the expression of receptors that are involved in antigen presentation. When mononuclear/phagocytic cells are activated by IL-4, IL-13, IL-10, and M-CSF, they differentiate into the M2 phenotype. Tumor-derived molecules, such as TGF-β and M-CSF, can polarize glioma-infiltrating microglia/microphages (MMs) toward the M2 phenotype and accordingly stimulate the production of anti-inflammatory molecules. Some other glioma-derived molecules, such as MCP-1 and VEGF, can recruit myeloid cells into the tumor site. Published with permission from Li and Graeber [29].