The Contribution of Vascular Endothelial Growth Factor to the Induction of Regulatory T-Cells in Malignant Effusions
It has been suggested that immunosuppressive cytokines such as transforming growth factor β (TGF-β) and interleukin 10 play an important role in the induction and/or maintenance of regulatory T-cells (Tregs) in patients with cancer. In the present study, whether or not vascular endothelial growth...
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Veröffentlicht in: | Anticancer research 2009-03, Vol.29 (3), p.881-888 |
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Zusammenfassung: | It has been suggested that immunosuppressive cytokines such as transforming growth factor β (TGF-β) and interleukin 10 play
an important role in the induction and/or maintenance of regulatory T-cells (Tregs) in patients with cancer. In the present
study, whether or not vascular endothelial growth factor (VEGF) contributes to the induction and/or maintenance of Tregs was
examined, because of experience with a patient in whom a positive correlation between VEGF concentration and the percentage
of Tregs (% Tregs) among the total CD4 + T-cells in the pleural effusion was found during dendritic cell activated lymphocyte therapy. CD4 + CD25 high T-cells were estimated as Tregs in the present study. In an in vitro experimental system, VEGF-containing malignant effusions
increased the % Tregs in autologous peripheral blood mononuclear cells (PBMCs), which could be suppressed by the addition
of a humanized monoclonal anti-VEGF antibody (bevacizumab [Avastin]). When VEGF-producing hepatic carcinoma cells were mix-cultured
with PBMCs, the % Tregs increased and this increase was also suppressed by the addition of bevacizumab. Whether or not bevacizumab
can affect the % Tregs of PBMCs in patients with colon cancer was also examined. Three out of four patients showed a significant
decrease of the % Tregs after intravenous injection of bevacizumab. Interestingly, the expression of VEGF receptor-2 (VEGFR-2)
was higher in Tregs than in other CD4 + T-cells. Taken together, the data presented here indicate a contribution of VEGF to induction and/or maintenance of Tregs
in patients with cancer. |
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ISSN: | 0250-7005 1791-7530 |