Figure 4.

Cytokine and chemokine expression by irradiated tumor cells, recruitment of immune cells and cytokine expression of the involved immune cells. Tumor cells express a plethora of soluble factors, cytokines and chemokines, and after irradiation, the secretion profile is modified. On the one hand, proinflammatory cytokines, like interleukin-6 (IL-6), IL-8, IL-12p70, tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), and IL-1α, are increasingly expressed in tumor cells models in vitro and in vivo. On the other hand, the expression of immune-suppressive soluble factors is modified. IL-10 and IL-1β expression is increased, but secretion of vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) is reduced. Further, chemokines, like CXCL16, are increasingly expressed and initiate recruitment of natural killer (NK) cells and other immune cells. The secretion of the damage-associated molecular pattern molecule high mobility group box 1 (HMGB1) is elevated as well in irradiated tumor cells, which leads to a activation of immune cells via the toll-like receptor 4 (TLR4), recruitment of immune cells via chemokine receptor CXCR4, as well as modification of cytokine expression of peripheral blood mononuclear cells.