PMID- 17086423
OWN - NLM
STAT- MEDLINE
DCOM- 20070605
LR  - 20240426
IS  - 0340-7004 (Print)
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Linking)
VI  - 56
IP  - 6
DP  - 2007 Jun
TI  - Vascular endothelial growth factor inhibits the function of human mature 
      dendritic cells mediated by VEGF receptor-2.
PG  - 761-70
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells and play a 
      central role in the host-antitumor immunity. Since it has been reported that 
      vascular endothelial growth factor (VEGF) inhibits the functional maturation of 
      immature-DCs and impairs DC differentiation, it is important to elucidate the 
      mechanisms of VEGF-induced DC-dysfunction. To investigate the effects of VEGF 
      against human mature DCs, we investigated how VEGF affects mature DCs with 
      regards to phenotype, induction of apoptosis, IL-12(p70) production and the 
      antigen-presenting function evaluated by allogeneic mixed leukocyte reaction 
      (allo-MLR). We generated monocyte-derived DCs matured with lipopolysaccharide, 
      OK-432 or pro-inflammatory cytokine cocktails. As a result, VEGF treatment did 
      not alter the mature DCs with regard to phenotype, IL-12(p70) production and 
      induction of apoptosis. As a novel and important finding, VEGF inhibited the 
      ability of mature DCs to stimulate allogeneic T cells. Furthermore, this 
      VEGF-induced DC dysfunction was mainly mediated by VEGF receptor-2 (VEGF R2). 
      These observations were confirmed by the findings that the VEGF-induced DC 
      dysfunction was recovered by anti-human VEGF neutralizing mAb or anti-human VEGF 
      R2 blocking mAb, and that placenta growth factor (PlGF), VEGF R1-specific ligand, 
      did not have any effect against mature DCs. Some modalities aiming at reversing 
      mature-DC dysfunction induced by VEGF will be needed in order to induce the 
      effective antitumor immunity.
FAU - Mimura, Kousaku
AU  - Mimura K
AD  - First Department of Surgery, University of Yamanashi, 1110 shimokato, Chuo-city, 
      Yamanashi 409-3898, Japan.
FAU - Kono, Koji
AU  - Kono K
FAU - Takahashi, Akihiro
AU  - Takahashi A
FAU - Kawaguchi, Yoshihiko
AU  - Kawaguchi Y
FAU - Fujii, Hideki
AU  - Fujii H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061104
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 187348-17-0 (Interleukin-12)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
SB  - IM
MH  - Antigen Presentation/*immunology
MH  - Apoptosis/immunology
MH  - Dendritic Cells/*immunology
MH  - Flow Cytometry
MH  - Humans
MH  - Interleukin-12/biosynthesis
MH  - Lymphocyte Culture Test, Mixed
MH  - Phenotype
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vascular Endothelial Growth Factor A/*immunology
MH  - Vascular Endothelial Growth Factor Receptor-2/*immunology
PMC - PMC11030780
EDAT- 2006/11/07 09:00
MHDA- 2007/06/06 09:00
PMCR- 2006/11/04
CRDT- 2006/11/07 09:00
PHST- 2006/03/21 00:00 [received]
PHST- 2006/10/10 00:00 [accepted]
PHST- 2006/11/07 09:00 [pubmed]
PHST- 2007/06/06 09:00 [medline]
PHST- 2006/11/07 09:00 [entrez]
PHST- 2006/11/04 00:00 [pmc-release]
AID - 234 [pii]
AID - 10.1007/s00262-006-0234-7 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2007 Jun;56(6):761-70. doi: 10.1007/s00262-006-0234-7. 
      Epub 2006 Nov 4.