Abstract |
It has been suggested that immunosuppressive cytokines such as transforming growth factor beta ( TGF-beta) 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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Authors | Junji Wada, Hiroyuki Suzuki, Ryouta Fuchino, Akio Yamasaki, Shuntaro Nagai, Kousuke Yanai, Kenichiro Koga, Masafumi Nakamura, Masao Tanaka, Takashi Morisaki, Mitsuo Katano |
Journal | Anticancer research
(Anticancer Res)
Vol. 29
Issue 3
Pg. 881-8
(Mar 2009)
ISSN: 0250-7005 [Print] Greece |
PMID | 19414323
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiogenesis Inhibitors
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
- Bevacizumab
- Vascular Endothelial Growth Factor Receptor-2
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Topics |
- Adult
- Aged
- Angiogenesis Inhibitors
(therapeutic use)
- Antibodies, Monoclonal
(therapeutic use)
- Antibodies, Monoclonal, Humanized
- Bevacizumab
- Dendritic Cells
(transplantation)
- Enzyme-Linked Immunosorbent Assay
- Female
- Flow Cytometry
- Humans
- Immunotherapy
- Male
- Middle Aged
- Neoplasms
(immunology, therapy)
- Pleural Effusion, Malignant
(immunology, therapy)
- T-Lymphocytes, Regulatory
(immunology)
- Vaccination
- Vascular Endothelial Growth Factor A
(antagonists & inhibitors, physiology)
- Vascular Endothelial Growth Factor Receptor-2
(metabolism)
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