Circulating IL-35 in pancreatic ductal adenocarcinoma patients

Hum Immunol. 2014 Jan;75(1):29-33. doi: 10.1016/j.humimm.2013.09.018. Epub 2013 Oct 11.


IL-35 is a novel inhibitory cytokine that is mainly produced by regulatory T-cells (Tregs) and is required for Treg-mediated immunosuppression. However, the plasma levels of IL-35 in patients with pancreatic ductal adenocarcinoma (PDAC) have never been investigated. In this study, we found that plasma IL-35 levels more significantly increased in PDAC patients than in normal controls (134.53 ± 92.45 pg/mL vs. 14.26 ± 6.56 pg/mL). IL-35 mRNA levels were positively correlated with plasma IL-35 levels (EBI3, R = 0.925, p<0.01; p35, R = 0.916, p<0.01). Furthermore, IL-35 expression levels were associated with lymph node metastasis (p = 0.001) and late tumor stage (p = 0.002). For the resected patients, high IL-35 expression levels were associated with large tumor size (p<0.01), higher TNM classification T staging (p<0.05), and late tumor stage (p<0.05). In conclusion, circulating IL-35 in PDAC patients significantly increased, suggesting that regulating the expression of IL-35 may provide a new possible target for the treatment of PDAC patients, especially for the resectable ones.

Keywords: EBI3; Epstein–Barr virus-induced gene 3; PBMCs; PDAC; Tregs; pancreatic ductal adenocarcinoma; peripheral blood mononuclear cells; regulatory T-cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Pancreatic Ductal / blood*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / pathology
  • Case-Control Studies
  • Female
  • Humans
  • Interleukin-12 Subunit p35 / blood
  • Interleukin-12 Subunit p35 / genetics
  • Interleukins / blood*
  • Interleukins / genetics
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens
  • Neoplasm Staging
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • RNA, Messenger / genetics


  • EBI3 protein, human
  • Interleukin-12 Subunit p35
  • Interleukins
  • Minor Histocompatibility Antigens
  • RNA, Messenger
  • interleukin-35, human