Context‐dependent role of IL‐18 in cancer biology and counter‐regulation by IL‐18BP. Issue 4 (29th December 2014)

• Record Type: Journal Article
• Authors: Fabbi, Marina; Carbotti, Grazia; Ferrini, Silvano
• Is Part Of: Journal of leukocyte biology. Volume 97:Issue 4(2015)
• Page Start: 665
• Page End: 675
• Publication Date: 2014-12-29
• Subjects: immune regulation -- cancer immunotherapy -- Th1 response; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.5RU0714-360RR
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Review of the dual role of IL‐18 and IL‐18BP in cancer therapy based on specific tumor characteristics. Abstract : IL‐18 is a proinflammatory and immune regulatory cytokine, member of the IL‐1 family. IL‐18 was initially identified as an IFN‐ γ ‐inducing factor in T and NK cells, involved in Th1 responses. IL‐18 is produced as an inactive precursor (pro‐IL‐18) that is enzymatically processed into a mature form by Casp1. Different cells, such as macrophages, DCs, microglial cells, synovial fibroblasts, and epithelial cells, express pro‐IL‐18, and the production of bioactive IL‐18 is mainly regulated at the processing level. PAMP or DAMP molecules activate inflammasomes, which trigger Casp1 activation and IL‐18 conversion. The natural inhibitor IL‐18BP, whose production is enhanced by IFN‐ γ and IL‐27, further regulates IL‐18 activity in the extracellular environment. Inflammasomes and IL‐18 represent double‐edged swords in cancer, as their activation may promote tumor development and progression or oppositely, enhance anti‐tumor immunity and limit tumor growth. IL‐18 has shown anti‐tumor activity in different preclinical models of cancer immunotherapy through the activation of NK and/or T cell responses and has been tested in clinical studies in cancer patients. However, the dual role of IL‐18 in different experimental tumor models and human cancers raises critical issues on its therapeutic use in cancer. This review will summarize the biology of the IL‐18/IL‐18R/IL‐18BP system and will address the role of IL‐18 and its inhibitor, IL‐18BP, in cancer biology and immunotherapy.