Fig. 2.

Glioma-microglia synergies drive a self-amplifying process that spirals out of control. Glioma and microglial cells have a symbiotic relationship that becomes highly skewed in favor of the glioma. The immunosuppressive microenvironment created by molecules such as TGF-β, FasL, and IL-10 polarizes glioma-infiltrating microglia toward the M2 phenotype (cf. Fig. 1). Glioma (red) produces chemotactic factors, such as MCP-1, resulting in the recruitment of microglia. Glioma further promotes the proliferation of microglia. In turn, microglia (purple) promote glioma angiogenesis as well as glioma cell invasion. The cross talk between glioma and microglia is governed by multiple paracrine loops formed by glioma and microglia released molecules and their receptors, as indicated by superscript (P) in the figure. In addition, some of the molecules act in an autocrine fashion, as indicated by the superscript (A) and regulate either glioma or microglia behavior.