Distribution of Th17 cells and FoxP3(+) regulatory T cells in tumor-infiltrating lymphocytes, tumor-draining lymph nodes and peripheral blood lymphocytes in patients with gastric cancer

Cancer Sci. 2010 Sep;101(9):1947-54. doi: 10.1111/j.1349-7006.2010.01624.x.


Although Th17 cells reportedly play critical roles in the development of autoimmunity and allergic reactions, information on Th17 cells in cancer-bearing hosts is still limited. In the present study, we investigated the distribution of Th17 cells in relation to regulatory T cells (Treg) in the tumor-infiltrating lymphocytes (TILs), regional lymph node lymphocytes, and peripheral blood lymphocytes of gastric cancer patients. Interleukin (IL)-17-producing CD4(+) cells as Th17 cells and CD4(+)CD25(+)FoxP3(+) cells as Treg were evaluated by flow cytometry and expressed as a percentage of the total CD4(+) cells, in addition to performing a Th1/Th2 balance assay. Moreover, immunohistochemical staining for IL-17 and FoxP3 were performed. In TILs from patients with early disease (n = 27), the frequency of Th17 cells was significantly higher than that in the normal gastric mucosa (23.7 ± 8.9 vs 4.5 ± 3.1%). In TILs from patients with advanced disease (n = 28), the frequency of Th17 cells was also significantly higher, but lower compared to early disease, than that in the normal gastric mucosa (15.1 ± 6.2 vs 4.0 ± 2.0%). This observation for Th17 cell-distribution was also confirmed by immunohistochemistry. When the ratio of Th17/Treg in TILs was evaluated in individual cases, it was more markedly increased in early than in advanced disease. In conclusion, the accumulation of Th17 cells as well as Treg in the tumor microenvironment of gastric cancer occurred in early disease and then the infiltration of Th17 cells gradually decreased according to the disease progression, in contrast to increased Treg.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunohistochemistry
  • Interleukin-17 / metabolism
  • Interleukin-23 / metabolism
  • Interleukins / metabolism
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th1-Th2 Balance
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-17
  • Interleukin-23
  • Interleukins
  • interleukin-21