Schematic diagram of the IL-6/JAK/STAT3 signaling pathway activation in mouse liver macrophages. (IMAGE)

China Anti-Cancer Association

Schematic diagram of the IL-6/JAK/STAT3 signaling pathway activation in mouse liver macrophages.

Caption

Schematic diagram of the IL-6/JAK/STAT3 signaling pathway activation in mouse liver macrophages. IRs, inhibitory receptors (IRs); ICIs, immune checkpoint inhibitors; IL-6, interleukin-6; ALT, alanine transaminase (ALT). In mice with immune-related adverse events (irAEs), EGFR is expressed on the surface of liver macrophages, which also harbor immunosuppressive receptors. When osimertinib is administered in combination with immune checkpoint inhibitors (ICIs), phosphorylation of EGFR (wild-type) on the surface of liver macrophages is inhibited and the IL-6/JAK/STAT3 signaling pathway is activated, leading to an increase in the release of cytokines into the serum, resembling a "cytokine storm." Notably, the addition of ruxolitinib, a small molecule inhibitor of JAK1/JAK2, to block the IL-6/JAK/STAT3 signaling pathway resulted in a significant decrease in the levels of these cytokines in the serum.

Credit

Cancer Biology & Medicine

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