Circulating IL-35 in pancreatic ductal adenocarcinoma patients

Abstract

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.