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

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. 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. 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. 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.