Human ovarian carcinoma cells generate CD4(+)CD25(+) regulatory T cells from peripheral CD4(+)CD25(-) T cells through secreting TGF-beta

Cancer Lett. 2007 Aug 8;253(1):144-53. doi: 10.1016/j.canlet.2007.01.024. Epub 2007 Mar 13.

Abstract

Increased CD4(+)CD25(+) regulatory T cells predicted poor prognosis in ovarian carcinoma patients. This study aimed to define whether soluble substances secreted by ovarian carcinoma could up-regulate the proportion of CD4(+)CD25(+) regulatory T cells. Similar to TGF-beta, the low MWF (<50kDa) of supernatant derived from SKOV3 could convert part of freshly isolated CD4(+)CD25(-) T cells into CD25(+) population with similar characters as natural CD4(+)CD25(+) regulatory T cells. To deplete TGF-beta in the low MWF by neutralizing anti-TGF-beta would eliminate this transformation phenomenon. These results indicate that TGF-beta secreted by ovarian carcinoma cells owns vital function in the process of converting peripheral CD4(+)CD25(-) T cells into CD4(+)CD25(+) regulatory T cells, which may provide one immunotherapeutic target for ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Line, Tumor
  • Female
  • Forkhead Transcription Factors / genetics
  • Humans
  • Interleukin-2 Receptor alpha Subunit / metabolism*
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / metabolism*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Transforming Growth Factor beta / metabolism*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit
  • Transforming Growth Factor beta