Il18, an inflammasome-induced pro-inflammatory cytokine, is a member of the IL-1 family. It enhances T-and NK-cell activity, stimulates IFNγ production, and facilitates type 1 immune responses. It binds to specific receptors (IL18r and NCC) and is involved in multiple biological processes [1,2,3].

In the tumor microenvironment (TME), IL18 is upregulated and mostly bound to IL18BP. Blocking the IL18BP:IL18 interaction using an anti-IL18BP antibody can release IL18, leading to potent T-and NK-cell activation, tumor growth inhibition, and increased survival in mouse tumor models [1].

In the pancreas, IL18 signaling via different receptors on acinar and β cells is crucial for islet β cell development, insulin secretion, and maintaining β cell function and homeostasis. Deficiency of its receptors reduces islet size, β cell proliferation, and insulin secretion while increasing β cell apoptosis [2].

In summary, Il18 plays essential roles in immune regulation, especially in T-and NK-cell activation, and in maintaining pancreatic β cell function. Mouse models, as in the anti-IL18BP-treated tumor models and receptor-deficient pancreas models, have revealed its significance in cancer immunotherapy and diabetes-related pancreatic function, respectively [1,2].