期刊
PANCREAS
卷 43, 期 3, 页码 470-477出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MPA.0000000000000055
关键词
IL-22; IL-22(+)CD4(+) T cells; T(H)22 cells; STAT-3; pancreatic cancer
资金
- National Natural Science Foundation of China [81072439, 81372242]
- Logistics Research Projects of PLA [CWS11J051]
- National High Technology Research and Development Program of China (863 Program) [2012AA021105]
- Research Special Fund for Public Welfare Industry of Health [201202007]
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 (T(H)22) cells (IL-22(+)IFN--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 T(H)22 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 T(H)22 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.
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