Emerging Roles for Interleukin-18 in the Gastrointestinal Tumor Microenvironment

Interleukin (IL)-18, a member of the IL-1 family of cytokines, has emerged as a key regulator of mucosal homeostasis within the gastrointestinal tract. Like other members of this family, IL-18 is secreted as an inactive protein and is processed into its active form by caspase-1, although other contributors to precursor processing are emerging. Numerous studies have evaluated the role of IL-18 within the gastrointestinal tract using genetic or complementary pharmacological tools and have revealed multiple roles in tumorigenesis. Most striking among these are the divergent roles for IL-18 in colon and gastric cancers. Here, we review our current understanding of IL-18 biology and how this applies to colorectal and gastric cancers.