The contribution of vascular endothelial growth factor to the induction of regulatory T- cells in malignant effusions

Junji Wada, Hiroyuki Suzuki, Ryouta Fuchino, Akio Yamasaki, Shuntaro Nagai, Kousuke Yanai, Kenichiro Koga, Masafumi Nakamura, Masao Tanaka, Takashi Morisaki, Mitsuo Katano

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Abstract

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+CD25high 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 the 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.

Original languageEnglish
Pages (from-to)881-888
Number of pages8
JournalAnticancer research
Volume29
Issue number3
Publication statusPublished - Mar 1 2009

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Wada, J., Suzuki, H., Fuchino, R., Yamasaki, A., Nagai, S., Yanai, K., ... Katano, M. (2009). The contribution of vascular endothelial growth factor to the induction of regulatory T- cells in malignant effusions. Anticancer research, 29(3), 881-888.