title: A protective role of IL-37 in cancer: a new hope for cancer patients.
abstract: IL-37 is a cytokine belonging to the IL-1 family. Although discovered in silico in 2000, significant advances in the understanding of its biology were made only in recent years. It is a member of the family with potent anti-inflammatory and immunosuppressive properties. It is produced as a precursor without a classic signal peptide. The precursor is cleaved into mature form in the cytoplasm by caspase-1. A small fraction of the cleaved IL-37 binds SMAD-3, translocates to the nucleus, and suppresses transcription of several proinflammatory genes. Both precursor and cleaved forms of IL-37 are secreted. They bind IL-18Rα chain (also used by IL-18 as a receptor subunit) and recruit Toll/IL-1R (TIR)-8 for transducing intracellular signaling. TIR-8 is a member of the IL-1 receptor family (IL-1RF) and was previously known as an orphan receptor. IL-37 suppresses activation of NF-κB and MAPK and activates Mer-PTEN-DOK pathway. It negatively regulates signaling mediated by TLR agonists, proinflammatory cytokines, and IL-1RF ligands. It also affects cell metabolism by inhibiting mTOR, GSK-3α/β, and activating AMPK. Despite having the ability to dampen host's immune responses, the cytokine has been shown to exert antitumor effects, and it has been suggested that it may act as a prognostic marker in a variety of human cancers. Recent studies have suggested that IL-37 may represent a novel therapeutic tool in patients with cancer. In this review, we provide an overview of the cytokine biology, discuss recent advances made in unraveling its anti-cancer effects, and suggest guidelines for future research.
authors.affiliation: Laboratory of Innate Immunity, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada.|Department of Microbiology, Infectiology and Immunology, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada.|Centre Hospitalier Universitaire, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada; and.
authors.forename: Ayoub
authors.initials: A
authors.lastname: Abulkhir
authors.affiliation: Laboratory of Innate Immunity, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada.|Department of Microbiology, Infectiology and Immunology, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada.|Centre Hospitalier Universitaire, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada; and.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Samarani
authors.affiliation: Centre Hospitalier Universitaire, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada; and.
authors.forename: Devendra
authors.initials: D
authors.lastname: Amre
authors.affiliation: Centre Hospitalier Universitaire, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada; and.
authors.forename: Michel
authors.initials: M
authors.lastname: Duval
authors.affiliation: Centre Hospitalier Universitaire, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada; and.
authors.forename: Elie
authors.initials: E
authors.lastname: Haddad
authors.affiliation: Centre Hospitalier Universitaire, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada; and.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sinnett
authors.affiliation: Centre Hospitalier Universitaire, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada; and.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Leclerc
authors.affiliation: Centre Hospitalier Universitaire de Québec Research Center, Quebec City, Quebec, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Diorio
authors.affiliation: Laboratory of Innate Immunity, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada; ali.ahmad@recherche-ste-justine.qc.ca.|Department of Microbiology, Infectiology and Immunology, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada.|Centre Hospitalier Universitaire, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada; and.
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmad
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D020011:Protective Agents / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007378:Interleukins; D020011:Protective Agents
keywords: IL-18; IL-18BP; IL-18Rα; SIGIRR; TIR-8