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Medical Oncology

, 33:68 | Cite as

The role of IL-37 in cancer

  • Vivi A. Ding
  • Ziwen Zhu
  • Huaping Xiao
  • Mark R. Wakefield
  • Qian Bai
  • Yujiang FangEmail author
Review Article

Abstract

Interleukin 37 (IL-37) is a new member of the IL-1 family which all have a similar β-barrel structure. Since its discovery, IL-37 has been studied extensively in immunological field. It has been established that IL-37 possesses anti-inflammatory characteristics both in innate immune response as well as in acquired immune responses by downregulating pro-inflammatory molecules. This review will discuss the role of IL-37 in immunological processes and neoplastic pathogenesis.

Keywords

IL-37 Immunity Cancer 

Notes

Acknowledgments

This study was supported by grants from Des Moines University for Yujiang Fang (IOER 05-14-01, IOER 112-3749, and IOER 112-3114).

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest.

References

  1. 1.
    Smith DE, Renshaw BR, Ketchem RR, Kubin M, Garka KE, Sims JE. Four new members expand the interleukin-1 superfamily. J Biol Chem. 2000;275(2):1169–75.CrossRefPubMedGoogle Scholar
  2. 2.
    Dinarello CA, editor. Overview of the interleukin-1 family of ligands and receptors. Seminars in immunology. Amsterdam: Elsevier; 2013.Google Scholar
  3. 3.
    Quirk S, Agrawal DK. Immunobiology of IL-37: mechanism of action and clinical perspectives. Expert Rev Clin Immunol. 2014;10(12):1703–9.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Dinarello C, Arend W, Sims J, Smith D, Blumberg H, O’Neill L, et al. IL-1 family nomenclature. Nat Immunol. 2010;11(11):973.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Van de Veerdonk FL, Netea MG. New insights in the immunobiology of IL-1 family members. Front Immunol. 2013;4(167):1–11.Google Scholar
  6. 6.
    Nold MF, Nold-Petry CA, Zepp JA, Palmer BE, Bufler P, Dinarello CA. IL-37 is a fundamental inhibitor of innate immunity. Nat Immunol. 2010;11(11):1014–22.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Busfield S, Comrack C, Yu G, Chickering T, Smutko J, Zhou H, et al. Identification and gene organization of three novel members of the IL-1 family on human chromosome 2. Genomics. 2000;66(2):213–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Kumar S, McDonnell PC, Lehr R, Tierney L, Tzimas MN, Griswold DE, et al. Identification and initial characterization of four novel members of the interleukin-1 family. J Biol Chem. 2000;275(14):10308–14.CrossRefPubMedGoogle Scholar
  9. 9.
    Pan G, Risser P, Mao W, Baldwin DT, Zhong AW, Filvaroff E, et al. IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp. Cytokine. 2001;13(1):1–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Taylor SL, Renshaw BR, Garka KE, Smith DE, Sims JE. Genomic organization of the interleukin-1 locus. Genomics. 2002;79(5):726–33.CrossRefPubMedGoogle Scholar
  11. 11.
    Kumar S, Hanning CR, Brigham-Burke MR, Rieman DJ, Lehr R, Khandekar S, et al. Interleukin-1F7B (IL-1H4/IL-1F7) is processed by caspase-1 and mature IL-1F7B binds to the IL-18 receptor but does not induce IFN-γ production. Cytokine. 2002;18(2):61–71.CrossRefPubMedGoogle Scholar
  12. 12.
    Boraschi D, Lucchesi D, Hainzl S, Leitner M, Maier E, Mangelberger D, et al. IL-37: a new anti-inflammatory cytokine of the IL-1 family. Eur Cytokine Netw. 2011;22(3):127–47.PubMedGoogle Scholar
  13. 13.
    Luo Y, Cai X, Liu S, Wang S, Nold-Petry CA, Nold MF, et al. 171: IL-37 suppresses contact hypersensitivity by inducing tolerogenic dendritic cells. Cytokine. 2013;63(3):283.CrossRefGoogle Scholar
  14. 14.
    Gao W, Kumar S, Lotze MT, Hanning C, Robbins PD, Gambotto A. Innate immunity mediated by the cytokine IL-1 homologue 4 (IL-1H4/IL-1F7) induces IL-12-dependent adaptive and profound antitumor immunity. J Immunol. 2003;170(1):107–13.CrossRefPubMedGoogle Scholar
  15. 15.
    Bufler P, Gamboni-Robertson F, Tania A, Soo-Hyun K, Dinarello CA. Interleukin-1 homologues IL-1F7b and IL-18 contain functional mRNA instability elements within the coding region responsive to lipopolysaccharide. Biochem J. 2004;381(2):503–10.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Bulau A-M, Nold MF, Li S, Nold-Petry CA, Fink M, Mansell A, et al. Role of caspase-1 in nuclear translocation of IL-37, release of the cytokine, and IL-37 inhibition of innate immune responses. Proc Natl Acad Sci. 2014;111(7):2650–5.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Martinon F, Tschopp J. Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ. 2007;14(1):10–22.CrossRefPubMedGoogle Scholar
  18. 18.
    Novick D, Kim S-H, Fantuzzi G, Reznikov LL, Dinarello CA, Rubinstein M. Interleukin-18 binding protein: a novel modulator of the Th1 cytokine response. Immunity. 1999;10(1):127–36.CrossRefPubMedGoogle Scholar
  19. 19.
    Akira S. The role of IL-18 in innate immunity. Curr Opin Immunol. 2000;12(1):59–63.CrossRefPubMedGoogle Scholar
  20. 20.
    Bufler P, Azam T, Gamboni-Robertson F, Reznikov LL, Kumar S, Dinarello CA, et al. A complex of the IL-1 homologue IL-1F7b and IL-18-binding protein reduces IL-18 activity. Proc Natl Acad Sci. 2002;99(21):13723–8.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Magne D, Palmer G, Barton JL, Mézin F, Talabot-Ayer D, Bas S, et al. The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes. Arthritis Res Ther. 2006;8(3):R80.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wald D, Qin J, Zhao Z, Qian Y, Naramura M, Tian L, et al. SIGIRR, a negative regulator of Toll-like receptor–interleukin 1 receptor signaling. Nat Immunol. 2003;4(9):920–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Xiao H, Gulen MF, Qin J, Yao J, Bulek K, Kish D, et al. The Toll–interleukin-1 receptor member SIGIRR regulates colonic epithelial homeostasis, inflammation, and tumorigenesis. Immunity. 2007;26(4):461–75.CrossRefPubMedGoogle Scholar
  24. 24.
    Nold-Petry CA, Lo CY, Rudloff I, Elgass KD, Li S, Gantier MP, et al. IL-37 requires the receptors IL-18R [alpha] and IL-1R8 (SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction. Nat Immunol. 2015;16(4):354–65.CrossRefPubMedGoogle Scholar
  25. 25.
    Li S, Neff CP, Barber K, Hong J, Luo Y, Azam T, et al. Extracellular forms of IL-37 inhibit innate inflammation in vitro and in vivo but require the IL-1 family decoy receptor IL-1R8. Proc Natl Acad Sci. 2015;112(8):2497–502.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Sharma S, Kulk N, Nold MF, Gräf R, Kim S-H, Reinhardt D, et al. The IL-1 family member 7b translocates to the nucleus and down-regulates proinflammatory cytokines. J Immunol. 2008;180(8):5477–82.CrossRefPubMedGoogle Scholar
  27. 27.
    Nold MF, Nold-Petry CA, Lo C, Li S, Rudloff I, Zepp JA, et al. 187: interleukin 37 employs the IL-1 family inhibitory receptor SIGIRR and the alpha chain of the IL-18 receptor to suppress innate immunity. Cytokine. 2013;63(3):287.CrossRefGoogle Scholar
  28. 28.
    Bulau A-M, Gruschka A, Schwaiger R, Dinarello CA, Bufler P. 30: anti-IL-37 antibody abrogates the protection in IL-37 transgenic mice to LPS-induced septic shock. Cytokine. 2013;63(3):250.CrossRefGoogle Scholar
  29. 29.
    Grimsby S, Jaensson H, Dubrovska A, Lomnytska M, Hellman U, Souchelnytskyi S. Proteomics-based identification of proteins interacting with Smad3: SREBP-2 forms a complex with Smad3 and inhibits its transcriptional activity. FEBS Lett. 2004;577(1):93–100.CrossRefPubMedGoogle Scholar
  30. 30.
    Chew V, Tow C, Teo M, Wong HL, Chan J, Gehring A, et al. Inflammatory tumour microenvironment is associated with superior survival in hepatocellular carcinoma patients. J Hepatol. 2010;52(3):370–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Zhao J-J, Pan Q-Z, Pan K, Weng D-S, Wang Q-J, Li J-J et al. Interleukin-37 mediates the antitumor activity in hepatocellular carcinoma: role for CD57+ NK cells. Sci Rep. 2014;4:5177.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.CrossRefPubMedGoogle Scholar
  33. 33.
    Wang S, An W, Yao Y, Chen R, Zheng X, Yang W, et al. Interleukin 37 expression inhibits STAT3 to suppress the proliferation and invasion of human cervical cancer cells. J Cancer. 2015;6(10):962.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    W-q Wang, Zhao D, Zhou Y-s Hu, X-y Sun Z-n, Yu G, et al. Transfer of the IL-37b gene elicits anti-tumor responses in mice bearing 4T1 breast cancer. Acta Pharmacol Sin. 2015;36(4):528–34.CrossRefGoogle Scholar
  35. 35.
    Haabeth O, Tveita AA, Fauskanger M, Schjesvold F, Lorvik KB, Hofgaard PO, et al. How do CD4 (+) T cells detect and eliminate tumor cells that either lack or express MHC class II molecules. Front Immunol. 2014;5:174.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Jiang Y, Wang Y, Liang L, Gao Y, Chen J, Sun Y, et al. IL-37 mediates the antitumor activity in renal cell carcinoma. Med Oncol. 2015;32(11):1–10.CrossRefGoogle Scholar
  37. 37.
    Ge G, Wang A, Yang J, Chen Y, Yang J, Li Y, et al. Interleukin-37 suppresses tumor growth through inhibition of angiogenesis in non-small cell lung cancer. J Exp Clin Cancer Res. 2016;35(1):1.CrossRefGoogle Scholar
  38. 38.
    Kachroo P, Lee M-H, Zhang L, Baratelli F, Lee G, Srivastava MK, et al. IL-27 inhibits epithelial-mesenchymal transition and angiogenic factor production in a STAT1-dominant pathway in human non-small cell lung cancer. J Exp Clin Cancer Res. 2013;32(1):1.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Vivi A. Ding
    • 1
  • Ziwen Zhu
    • 2
  • Huaping Xiao
    • 3
  • Mark R. Wakefield
    • 2
  • Qian Bai
    • 2
  • Yujiang Fang
    • 1
    • 2
    Email author
  1. 1.Department of Microbiology, Immunology & PathologyDes Moines UniversityDes MoinesUSA
  2. 2.Department of SurgeryUniversity of Missouri School of MedicineColumbiaUSA
  3. 3.The Affiliated Hospital of Xiangnan UniversityChenzhouChina

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