title: Th22 cell accumulation is associated with colorectal cancer development.
abstract: OBJECTIVE
  To investigate the expression of Th22 cells and related cytokines in colorectal cancer (CRC) tissues, and the probably mechanism.
  
  
  METHODS
  CRC tumor and paratumor tissues were collected to detect the expression levels of Th22 cells and of related cytokines by immunohistochemistry, flow cytometry and real-time quantitative polymerase chain reaction (RT-qPCR). Interleukin (IL)-22 alone or with a STAT3 inhibitor was co-cultured with RKO cells in vitro to study the effects of IL-22 on colon cancer cells. IL-22 alone or with a STAT3 inhibitor was injected into a BALB/c nude mouse model with subcutaneously transplanted RKO cells to study the effects of IL-22 on colon cancer growth.
  
  
  RESULTS
  The percentage of Th22 cells in the CD4(+) T subset was significantly higher in tumor tissues compared with that in paratumor tissues (1.47% ± 0.083% vs 1.23% ± 0.077%, P < 0.05) as determined by flow cytometry. RT-qPCR analysis revealed that the mRNA expression levels of IL-22, aryl hydrocarbon receptor, CCL20 and CCL22 were significantly higher in tumor tissues compared with those in paratumor tissues. CCL27 mRNA also displayed a higher expression level in tumor tissues compared with that in paratumor tissues; however, these levels were not significantly different (2.58 ± 0.93 vs 2.30 ± 0.78, P > 0.05). IL-22 enhanced colon cancer cell proliferation in vitro and displayed anti-apoptotic effects; these effects were blocked by adding a STAT3 inhibitor. IL-22 promoted tumor growth in BALB/c nude mice; however, this effect was reversed by adding a STAT3 inhibitor.
  
  
  CONCLUSIONS
  Th22 cells that accumulate in CRC may be associated with the chemotactic effect of the tumor microenvironment. IL-22 is associated with CRC development, most likely via STAT3 activation.
authors.affiliation: Yong-Hong Huang, Yun-Fei Cao, Zhi-Yuan Jiang, Sen Zhang, Feng Gao, Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Yong-Hong Huang, Yun-Fei Cao, Zhi-Yuan Jiang, Sen Zhang, Feng Gao, Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Cao
authors.affiliation: Yong-Hong Huang, Yun-Fei Cao, Zhi-Yuan Jiang, Sen Zhang, Feng Gao, Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Jiang
authors.affiliation: Yong-Hong Huang, Yun-Fei Cao, Zhi-Yuan Jiang, Sen Zhang, Feng Gao, Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Yong-Hong Huang, Yun-Fei Cao, Zhi-Yuan Jiang, Sen Zhang, Feng Gao, Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007378:Interleukins / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C494086:STAT3 protein, human
keywords: Colorectal cancer; Interleukin-22; STAT3; Th22 cells; Tumor microenvironment