Increased Intratumoral Interleukin 22 Levels and Frequencies of Interleukin 22–Producing CD4+ T Cells Correlate With Pancreatic Cancer Progression

Objective The objective of this study was to investigate the expression and clinical relevance of interleukin 22 (IL-22) and IL-22–producing CD4+ T cells (IL-22+CD4+ T cells) in pancreatic cancer (PC) tissues. Methods Interleukin 22 protein levels in PC tissues were measured by Western blot analysis and immunohistochemistry. The frequencies of IL-22+CD4+ T cells in tumors and peripheral blood from PC patients and control subjects were analyzed by flow cytometry. The association between IL-22 and phosphorylation of STAT-3 was investigated in in vitro model. Results Interleukin 22 protein was more highly expressed in PC tissues than in peritumoral and normal pancreatic tissues. The frequencies of all IL-22+CD4+ T cells and T helper 22 (TH22) cells (IL-22+IFN-&ggr;−IL-17-CD4+) were significantly higher in PC tissues than in the peripheral blood of PC patients and control subjects. It was observed that up-regulation pSTAT-3 and its downstream genes such as Bcl-2 and cyclin D1 in vitro. Finally, we found that increased intratumoral IL-22 expression and frequencies of TH22 and IL-22+CD4+ T cells were positively correlated with PC tumor-node-metastasis staging. Conclusions Increased intratumoral IL-22 levels, IL-22+CD4+ T cells, and TH22 cells are correlated with PC tumor-node-metastasis staging, suggesting that IL-22 and IL-22+CD4+ T cells may be related to tumor progression and are potential therapeutic targets in patients with PC.