title: VEGF directly suppresses activation of T cells from ascites secondary to ovarian cancer via VEGF receptor type 2.
abstract: BACKGROUND
  Vascular endothelial growth factor action in tumour angiogenesis is well characterised; nevertheless, it functions as a key element in the promotion of the immune system's evasion by tumours. We sought to investigate the possible direct effect of VEGF on T-cell activation and through which type of VEGF receptor it exerts this effect on cells isolated from ovarian cancer patients' ascites.
  
  
  METHODS
  T cells isolated from the ascites of ovarian cancer patients were cultured with anti-CD3 and IL-2, with or without VEGF for 14 days and the number of viable T cells was counted. Cytotoxic activity of cultured T cells and expression of VEGF receptor-2 (VEGFR-2), was assayed.
  
  
  RESULTS
  The addition of VEGF in cultures significantly reduced the number and proliferation rate of T cells in a dose-dependent manner and CD3(+) T cells expressed VEGFR-2 on their surface upon activation. Experiments with specific anti-VEGFR-2 antibodies revealed that the direct suppressive effect of VEGF on T-cell proliferation is mediated by VEGFR-2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells.
  
  
  CONCLUSIONS
  Our study showed that ascites-derived T cells secrete VEGF and express VEGFR-2 upon activation. Vascular endothelial growth factor directly suppresses T-cell activation via VEGFR-2.
authors.affiliation: Department of Clinical Therapeutics, Medical School, University of Athens, Alexandra Hospital, 80 Vas. Sofias Avenue, 115 28 Athens, Greece.
authors.forename: N G
authors.initials: NG
authors.lastname: Gavalas
authors.forename: M
authors.initials: M
authors.lastname: Tsiatas
authors.forename: O
authors.initials: O
authors.lastname: Tsitsilonis
authors.forename: E
authors.initials: E
authors.lastname: Politi
authors.forename: K
authors.initials: K
authors.lastname: Ioannou
authors.forename: A C
authors.initials: AC
authors.lastname: Ziogas
authors.forename: A
authors.initials: A
authors.lastname: Rodolakis
authors.forename: G
authors.initials: G
authors.lastname: Vlahos
authors.forename: N
authors.initials: N
authors.lastname: Thomakos
authors.forename: D
authors.initials: D
authors.lastname: Haidopoulos
authors.forename: E
authors.initials: E
authors.lastname: Terpos
authors.forename: A
authors.initials: A
authors.lastname: Antsaklis
authors.forename: M A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: A
authors.initials: A
authors.lastname: Bamias
mesh_terms: D001201:Ascites / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D010051:Ovarian Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000502:physiology*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2