IL-35, a double-edged sword in cancer

J Cell Biochem. 2020 Mar;121(3):2064-2076. doi: 10.1002/jcb.29441. Epub 2019 Oct 21.


Interleukin 35 (IL-35), a cytokine mainly produced by regulatory T cells (Treg cells), is composed of an Epstein-Barr virus-induced gene 3 β-chain and an IL-12 p35 α-chain. IL-35 causes tumorigenicity in cancer, protects cancer cells against apoptosis, and facilitates cancer progression. However, a few reports have referred to its contradictory roles in cancer prevention. Therefore, the exact purpose of this cytokine in cancer development has become a fundamental question that needs to be answered. In this review, we explain the structure of IL-35 and its receptors and their different signaling pathways. Finally, the function of IL-35 in some cancers and the possible application of this cytokine in approaches for cancer therapy have been discussed.

Keywords: IL-12 family; cancer; interleukin-35; regulatory B cells; regulatory T cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Interleukins / metabolism*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / prevention & control


  • Biomarkers, Tumor
  • Interleukins
  • interleukin-35, human
  • interleukin-35, mouse