title: Increased intratumoral interleukin 22 levels and frequencies of interleukin 22-producing CD4+ T cells correlate with pancreatic cancer progression.
abstract: 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-22CD4 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-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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the *Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, and †Institute of Immunology PLA, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Xu
authors.forename: Yichen
authors.initials: Y
authors.lastname: Tang
authors.forename: Shixiang
authors.initials: S
authors.lastname: Guo
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Tian
authors.forename: Bing
authors.initials: B
authors.lastname: Ni
authors.forename: Huaizhi
authors.initials: H
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D000097043:Interleukin-22
chemical_list: D019938:Cyclin D1; D007378:Interleukins; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22