title: Vascular endothelial growth factor-trap overcomes defects in dendritic cell differentiation but does not improve antigen-specific immune responses.
abstract: OBJECTIVE
  Induction of antitumor immune responses requires adequate function of dendritic cells. Dendritic cell defects in cancer patients have been implicated in tumor escape and the limited efficacy of cancer vaccines. Previous studies have shown that vascular endothelial growth factor (VEGF) plays a major role in abnormal dendritic cell differentiation and function in cancer. It has been proposed that inhibition of VEGF may result in improved immune responses. The goal of this study was to test this hypothesis.
  
  
  METHODS
  Fifteen patients with refractory solid tumors were enrolled into a phase I clinical trial of VEGF-Trap. Phenotype and function of different subsets of mononuclear cells were measured before and at different time points after the start of treatment.
  
  
  RESULTS
  VEGF-Trap treatment did not affect the total population of dendritic cells, their myeloid or plasmacytoid subsets, myeloid-derived suppressor cells (MDSC), or regulatory T cells. It significantly increased the proportion of mature dendritic cells. However, that improvement was not associated with an overall increase in immune responses to various antigens and mitogens. A subset analysis revealed significant improvement in immune responses in patients who had no increase in the proportion of MDSC. An improvement in immune responses was absent in patients with an increase in the proportion of MDSC.
  
  
  CONCLUSIONS
  Inhibition of VEGF signaling may improve differentiation of dendritic cells in cancer patients. However, it was not sufficient to improve immune responses. This shows multifaceted nature of immune deficiency and points out to the need for complex approach to modulation of immune reactivity in cancer.
authors: H. Lee Moffitt Cancer Center, University of South Florida, Tampa, Florida 33612, USA.
authors: Ingo
authors: I
authors: Fricke
authors: Noweeda
authors: N
authors: Mirza
authors: Jakob
authors: J
authors: Dupont
authors: Craig
authors: C
authors: Lockhart
authors: Autumn
authors: A
authors: Jackson
authors: Ji-Hyun
authors: JH
authors: Lee
authors: Jeffrey A
authors: JA
authors: Sosman
authors: Dmitry I
authors: DI
authors: Gabrilovich
mesh_terms: D000328:Adult; D000368:Aged; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor