Surface-bound TGF-β1 on effusion-derived exosomes participates in maintenance of number and suppressive function of regulatory T-cells in malignant effusions

Junji Wada, Hideya Onishi, Hiroyuki Suzuki, Akio Yamasaki, Shuntaro Nagai, Takashi Morisaki, Mitsuo Katano

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35 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3747-3757
Number of pages11
JournalAnticancer research
Volume30
Issue number9
Publication statusPublished - Sep 1 2010

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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