Increased CD4CD25+FOXP3+ regulatory T Cells in cancer patients from conversion of CD4+CD25- T cells through tumor-derived factors

Onkologie. 2008 May;31(5):243-8. doi: 10.1159/000121360. Epub 2008 Apr 10.

Abstract

Background: CD4+CD25+ regulatory T (Treg) cells play a pivotal role in the maintenance of the homeostatic balance of the immune system. The current study was conducted to evaluate the prevalence of CD4+CD25+ Treg cells in cancer patients and to identify possible mechanisms contributing to Treg cell expansion.

Materials and methods: The frequencies of CD4+CD25+FOXP3+ T cells in the peripheral blood mononuclear cells (PBMCs) of 62 cancer patients and 25 healthy individuals were determined by flow cytometry. The purified CD4+CD25- T cells were stimulated with malignant pleural effusion (MPE) or tumor cell-derived supernatants (TCS) from cancer patients in vitro. MPE/TCS-exposed CD4+ CD25- T cells were also characterized in terms of phenotype (CD4, CD25, and FOXP3 expression) and function (i.e. suppression assays).

Results: An increased population of CD4+ CD25+FOXP3+ T cells was detected in the peripheral blood of cancer patients, with no obvious difference between the adenocarcinoma group and the squamous carcinoma group. When stimulated with MPE or TCS, a fraction of natural CD4+CD25- T cells was converted into CD4+CD25+ FOXP3+ T cells which had the functional activity resembling natural CD4+CD25+ Treg cells with anergy and imm unosuppression.

Conclusion: The percentages of CD4+CD25+ FOXP3+ Treg cells in PBMCs of cancer patients are significantly increased. Tumor-derived factors such as TGF-betamay contribute to CD4+CD25+ Treg cell expansion in cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Communication / immunology
  • Cell Transformation, Neoplastic / immunology*
  • Humans
  • Leukocytes, Mononuclear / immunology*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Neoplasms / immunology*
  • Neoplasms / pathology*
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Cells, Cultured