A protective role of IL-37 in cancer: A new hope for cancer patients

Ayoub Abulkhir, Suzanne Samarani, Devendra Amre, Michel Duval, Elie Haddad, Daniel Sinnett, Jean Marie Leclerc, Caroline Diorio, Ali Ahmad

Research output: Contribution to journalReview articlepeer-review

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 cellmetabolismby 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.

Original languageEnglish (US)
Pages (from-to)395-406
Number of pages12
JournalJournal of Leukocyte Biology
Volume101
Issue number2
DOIs
StatePublished - Feb 2017

Keywords

  • IL-18
  • IL-18BP
  • IL-18Rα
  • SIGIRR
  • TIR-8

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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