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

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)

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 2009

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'The contribution of vascular endothelial growth factor to the induction of regulatory T- cells in malignant effusions'. Together they form a unique fingerprint.

Cite this