Surface-bound TGF-beta1 on effusion-derived exosomes participates in maintenance of number and suppressive function of regulatory T-cells in malignant effusions

Anticancer Res. 2010 Sep;30(9):3747-57.

Abstract

Background: This study analysed the contribution of malignant-effusion derived exosomes (Eff-Ex) to the number and function of regulatory T-cells (Treg) in malignant effusions.

Patients and methods: Eff-Ex were collected from the malignant effusions of 24 cancer patients. Peripheral blood mononuclear cells (PBMCs) were co-cultured with different concentrations of Eff-Ex. FOXP3(+) CD4(+) T-cells were defined as Treg. Expression of molecules on Eff-Ex was determined by flow cytometric analysis.

Results: The number of Treg decreased daily in parallel with the FOXP3 expression level. Purified Eff-Ex prevented the decreases in both Treg number and FOXP3 expression levels in a dose-dependent manner. Pre-treatment of Eff-Ex with a neutralizing mAb against TGF-β1 significantly reduced these effects and the suppressive function of Treg.

Conclusion: Elimination of Eff-Ex or control of Eff-Ex expressing TGF-β1 may be new therapeutic strategies in immunotherapy for advanced cancer patients with malignant effusions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Separation
  • Coculture Techniques
  • Enzyme-Linked Immunosorbent Assay
  • Exosomes / immunology*
  • Exosomes / metabolism
  • Flow Cytometry
  • Humans
  • Immunoblotting
  • Leukocytes, Mononuclear / immunology
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Pleural Effusion, Malignant / immunology*
  • Pleural Effusion, Malignant / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Transforming Growth Factor beta1 / immunology*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Transforming Growth Factor beta1