title: Accumulation of FoxP3+ T regulatory cells in the tumor microenvironment of human colorectal adenomas.
abstract: OBJECTIVE
  T regulatory cells (Tregs) play a critical important role for the occurrence and development of human tumors. Most human colorectal cancers (CRCs) develop from the preformed adenomas, this study is therefore designed to evaluate forkhead box P3 (FoxP3)+ Tregs in human colorectal adenomas.
  
  
  METHODS
  FoxP3+ Tregs in human colorectal adenomas were evaluated with immunohistochemistry (IHC) and real-time PCR, and compared to CRCs and normal tissues. In addition, the change of Treg immunosuppressive cytokine interleukin (IL)-10 was examined with IHC and real-time PCR.
  
  
  RESULTS
  increased FoxP3+Tregs were observed in the adenomatous stroma/epithelium and the density in colorectal adenomas, which was similar to that in the CRCs, significantly increased as compared to normal tissues. Numerous IL-10+cells were observed in the adenomatous stroma, but not in adenomatous epithelium, as compared with the controls. The density grading score of IL-10+ cells in the adenomas confirmed an increased density of IL-10+cells in the adenomatous/CRC stroma. Double IHCs with CD4/CD25 and IL-10/FoxP3 antibodies confirmed above observations and revealed that IL-10 was at least partially released from increased Tregs. Quantitative real-time PCR results confirmed that the expression levels of FoxP3 and IL-10 mRNAs in the adenomas were increased, which equivalent to that in the CRCs.
  
  
  CONCLUSIONS
  accumulation of FoxP3+ Tregs in the tumor microenvironment is an early event along the adenoma-carcinoma sequence, and might play a role in the regulation of host immune response to the initiation of CRC.
authors.affiliation: Research Group of Gastrointestinal Diseases, the Second Affiliated Hospital of Zhengzhou University, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hua
authors.affiliation: Research Group of Gastrointestinal Diseases, the Second Affiliated Hospital of Zhengzhou University, China; Laboratory of Molecular Cell Biology, Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.
authors.forename: Aping
authors.initials: A
authors.lastname: Yuan
authors.affiliation: Research Group of Gastrointestinal Diseases, the Second Affiliated Hospital of Zhengzhou University, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Research Group of Gastrointestinal Diseases, the Second Affiliated Hospital of Zhengzhou University, China.
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.affiliation: Research Group of Gastrointestinal Diseases, the Second Affiliated Hospital of Zhengzhou University, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.affiliation: Research Group of Gastrointestinal Diseases, the Second Affiliated Hospital of Zhengzhou University, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Pang
authors.affiliation: Research Group of Gastrointestinal Diseases, the Second Affiliated Hospital of Zhengzhou University, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Research Group of Gastrointestinal Diseases, the Second Affiliated Hospital of Zhengzhou University, China.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Goll
authors.affiliation: Research Group of Gastrointestinal Diseases, the Second Affiliated Hospital of Zhengzhou University, China; Faculty of Health, Nord-Trøndelag University College at Levanger, Norway. Electronic address: guanglin.cui@yahoo.com.
authors.forename: Guanglin
authors.initials: G
authors.lastname: Cui
mesh_terms: D000236:Adenoma / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000032:analysis / Q000235:genetics; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000032:analysis* / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; D012097:Repressor Proteins; D016753:Interleukin-10
keywords: Adenoma; Carcinoma; Colorectum; Forkhead box P3; Interleukin-10; Regulatory T cells