TY - JOUR
T1 - A protective role of IL-37 in cancer
T2 - A new hope for cancer patients
AU - Abulkhir, Ayoub
AU - Samarani, Suzanne
AU - Amre, Devendra
AU - Duval, Michel
AU - Haddad, Elie
AU - Sinnett, Daniel
AU - Leclerc, Jean Marie
AU - Diorio, Caroline
AU - Ahmad, Ali
N1 - Publisher Copyright:
© Society for Leukocyte Biology.
PY - 2017/2
Y1 - 2017/2
N2 - 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.
AB - 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.
KW - IL-18
KW - IL-18BP
KW - IL-18Rα
KW - SIGIRR
KW - TIR-8
UR - http://www.scopus.com/inward/record.url?scp=85011397664&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011397664&partnerID=8YFLogxK
U2 - 10.1189/jlb.5RU0816-341R
DO - 10.1189/jlb.5RU0816-341R
M3 - Review article
C2 - 27881603
AN - SCOPUS:85011397664
SN - 0741-5400
VL - 101
SP - 395
EP - 406
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 2
ER -