Fig. 6

Immunomodulatory effect of radiation on MDSCs. DNA damage resulted from radiation may activate two signaling pathways in MDSCs: cGAS-STING and JAK/STAT signaling pathways. Similar to signaling pathways in TAMs, JAK/STAT signaling and PI3K/AKT signaling pathway are activated in MDSCs caused by CSF-1/CSF-1R and CCL2/CCR2. Upon DNA damage, all of these damaged DNA including cytoplasmic DNA and mtDNA induced by IR can be recognized by cGAS, which then oligomerizes with DNA in the form of a 2:2 complex.^114,115,116 After binding to DNA, cGAS then exerts a catalytic role to promote the synthesis of the second messenger 2′3′-cyclic GMP–AMP (cGAMP). Binding of 2′3′-cGAMP stimulates STING and promotes the translocation to the Golgi which acivates TANK-binding kinase 1 (TBK1). TBK1 phosphorylates STING and promote the interferon regulatory factor 3 (IRF3) to translocate to the nucleus which triggers the expression of IFN-β gene. Parts of this figure were drawn with aid of Servier Medical Art (http://www.servier.com), licensed under a Creative Commons Attribution 3.0 Unported License