title: Conversion of intratumoral regulatory T cells by human gastric cancer cells is dependent on transforming growth factor-β1.
abstract: OBJECTIVE
  Regulatory T cells (Treg) inhibits immune responses mediated by T cells. This study aimed to investigate whether Treg are accumulated in human gastric cancer tissue and the mechanism of Treg induction by gastric cancer cells.
  
  
  METHODS
  Tissue infiltrated leukocytes from gastric adenocarcinomas were subjected to flow cytometry and immunohistochemistry. Percentage, phenotype, function, and clinical relevance of Treg were analyzed. TGF-β1 production by cancer cells was determined by Western blot and in vitro co-culture experiments were performed to mimic gastric cancer microenvironment.
  
  
  RESULTS
  The percentages of CD4(+) Foxp3(+) T cells in gastric cancer tissues were significantly higher than those from adjacent non-tumor gastric tissues (P < 0.05). The results of classical Treg phenotype and proliferation assay supported that the elevated CD4(+) Foxp3(+) T cells represents a suppressive Treg population. High proportion of Treg is correlated to advance TNM stage and reduced survival. Primary gastric cancer cells produced abundance of TGF-β1 which was responsible for conversion of Treg.
  
  
  CONCLUSIONS
  The proportion of functional Treg is elevated in human gastric cancer and related to poor prognosis. Gastric cancer cells directly convert CD4(+) naive T cells to Treg by TGF-β1, suggesting a possible mechanism through which tumor cells evade the immune system.
authors.affiliation: Department of Gastroenterology Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Lu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xuesong
authors.initials: X
authors.lastname: Wang
authors.forename: Jingwei
authors.initials: J
authors.lastname: Ma
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tong
authors.forename: Ke
authors.initials: K
authors.lastname: Wu
authors.forename: Guobin
authors.initials: G
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005753:Gastric Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053773:Transforming Growth Factor beta1