Increased intratumoral interleukin 22 levels and frequencies of interleukin 22-producing CD4+ T cells correlate with pancreatic cancer progression

• Published in: Pancreas Vol. 43; no. 3; p. 470
• Main Authors: Xu, Xuejun, Tang, Yichen, Guo, Shixiang, Zhang, Yi, Tian, Yi, Ni, Bing, Wang, Huaizhi
• Format: Journal Article
• Language: English
• Published: United States 01.04.2014
• Subjects: Blotting, Western; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; Cells, Cultured; Cyclin D1 - metabolism; Disease Progression; Female; Flow Cytometry; Humans; Immunohistochemistry; Interleukin-22; Interleukins - metabolism; Male; Middle Aged; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Phosphorylation; Proto-Oncogene Proteins c-bcl-2 - metabolism; STAT3 Transcription Factor - metabolism; T-Lymphocytes, Helper-Inducer - metabolism; T-Lymphocytes, Helper-Inducer - pathology; Up-Regulation
• ISSN: 1536-4828
• DOI: 10.1097/MPA.0000000000000055

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-22CD4 T cells) in pancreatic cancer (PC) tissues. Interleukin 22 protein levels in PC tissues were measured by Western blot analysis and immunohistochemistry. The frequencies of IL-22CD4 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. Interleukin 22 protein was more highly expressed in PC tissues than in peritumoral and normal pancreatic tissues. The frequencies of all IL-22CD4 T cells and T helper 22 (TH22) cells (IL-22IFN-γIL-17CD4) 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-22CD4 T cells were positively correlated with PC tumor-node-metastasis staging. Increased intratumoral IL-22 levels, IL-22CD4 T cells, and TH22 cells are correlated with PC tumor-node-metastasis staging, suggesting that IL-22 and IL-22CD4 T cells may be related to tumor progression and are potential therapeutic targets in patients with PC.