Figure 2.

IL-36 Signaling in cancer. IL-36 signaling is achieved through binding of the IL-36α, IL-36β or IL-36γ cytokines to the IL-36 Receptor (IL1RL2), along with the transmembrane accessory protein, IL-1RAcP. This binding may be inhibited through competitive binding of IL-36RA or IL-38. Agonist binding is followed by subsequent engagement and phosphorylation of intracellular signaling molecules to activate transcription factors such as NF-κB and AP-1. This promotes the observed anti-tumorigenic phenotype, which may be achieved by increased IFN-γ production, reduced immunosuppression and increased immune cell recruitment to the local tumor microenvironment.