Interleukin-18: Biology and Role in the Immunotherapy of Cancer

Interleukin-18 (IL-18) is an immunostimulatory cytokine belonging to the IL-1 family. IL-18 can regulate both innate and adaptive immune responses through its effects on natural killer (NK) cells, monocytes, dendritic cells, T cells, and B cells. IL-18 acts synergistically with other pro-inflammatory cytokines to promote interferon-γ (IFN-γ) production by NK cells, T cells, and possibly other cell types. Systemic administration of IL-18 has been shown to have significant antitumor activity in several preclinical animal models. Phase I clinical trials of recombinant human IL-18 have demonstrated that it can be safely administered to patients with advanced cancer. Biologic effects of IL-18 therapy include activation of monocytes, NK cells, and T cells and production of IFN-γ as well as other cytokines in vivo. A phase II study of IL-18 in patients with metastatic melanoma confirmed its safety but suggested limited efficacy of IL-18 monotherapy in this setting. IL-18 appears to act predominantly as a costimulatory cytokine and its optimal use for cancer immunotherapy may be in combination with other immunostimulatory cytokines, vaccines, or monoclonal antibodies. Keywords: Cytokine, immunotherapy, natural killer cell, T cell, rituximab, interferon-γ, Interleukin-18, IL-1 family, interleukin-12, carcinogenesis, MyD88, IRAK, TRAF6, ICAM-1, VCAM-1, endothelial cells, fibroblasts, antibodies, CD4+ T cells, MCA205, Gene Therapy, prostate specific antigen, adenovirus, Chemotherapy, Stem Cell Transplantation, STAT, CLINICAL TRIALS, Melanoma, monocytes, monoclonal antibodies, vaccines, chemotherapeutic agents