Distribution of CD4+CD25high regulatory T-cells in tumor-draining lymph nodes in patients with gastric cancer

J Surg Res. 2005 Mar;124(1):151-7. doi: 10.1016/j.jss.2004.10.004.


Background: Regulatory T-cells (T-regs) can inhibit the immune response mediated by T-cells. There is an increasing evidence that there is an increased proportion of T-regs in PBLs and tumor-infiltrating lymphocytes in several different human malignancies, although the mechanism remains unclear. In the present study, we evaluated the prevalence of CD4+CD25high T-regs in tumor-draining lymph nodes in patients with gastric cancers.

Materials and methods: Regional lymph nodes in the stomach of the patients with gastric cancer (n=44) were classified into N1 regional lymph nodes adjacent to the gastric tumor and N2 regional lymph nodes marginally distant from the tumor. The population of CD4+CD25high T-cells as a percentage of total CD4+ cells was evaluated by flow cytometric analysis with triple-color staining. Cytokine production (IL-10 and IFN-gamma) was evaluated by intracellular cytokine staining and the antiproliferative function of CD4+CD25+ cells positively selected by magnetic beads was measured by evaluating the proliferative activity of CD4+CD25- cells in response to anti-CD3 plus anti-CD28 in the presence of autologous CD4+CD25+ cells.

Results: The percentage of CD4+CD25high T-cells in N1 regional lymph nodes (3.1 +/- 0.3%) was significantly higher than that of control mesenteric lymph nodes (1.2 +/- 0.3%, P <0.01). Furthermore, a more extended area (N2) of regional lymph nodes, as well as adjacent lymph nodes (N1) to the tumors, was involved in an increased prevalence of CD4+CD25high T-cells according to the disease progression. The functional evaluations confirmed that CD4+CD25high T-cells derived from the lymph nodes have an inhibitory activity corresponding to T-regs.

Conclusions: The populations of CD4+CD25high T-cells in the regional lymph nodes in patients with gastric cancer were significantly higher in comparison to those in control lymph nodes. The increased prevalence of T-regs may be one of the explanations for impaired cell-mediated immunity in cancer-bearing hosts.

MeSH terms

  • Aged
  • CD4-Positive T-Lymphocytes / immunology*
  • Female
  • Humans
  • Lymph Nodes / immunology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Receptors, Interleukin-2 / immunology*
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / pathology
  • T-Lymphocytes / immunology*


  • Receptors, Interleukin-2