Dendritic cells and vascular endothelial growth factor in colorectal cancer: correlations with clinicobiological findings

Oncology. 2005;68(2-3):276-84. doi: 10.1159/000086784. Epub 2005 Jul 7.


Objective: Dendritic cells (DC) are central to the development of immune system responses. In a cohort of 54 patients affected by colorectal cancer, we prospectively investigated the number of peripheral blood (PB) DC type 1 (DC1) and type 2 (DC2) and correlated their counts and functionality to the stage of the disease and to vascular endothelial growth factor (VEGF) levels.

Results: At diagnosis, compared with healthy controls, patients presented reduced PBDC1 and PBDC2 numbers (p < 0.001). Moreover, in cancer patients, PBDC showed low levels of DC-associated antigens (HLA DR, p = 0.004; CD11c, p < 0.001; CD83, p = 0.01; CD86, p = 0.007 and Mannose receptor, p = 0.029), an upregulation of CXCR4 (p = 0.017) and a reduced T cell stimulation capability (p < 0.001). DC1 and DC2 loss was higher in stage D versus stage ABC patients (p = 0.003 and p = 0.002, respectively); surgery and chemotherapy appeared to attenuate a DC defect, although the restoration of normal PBDC levels is completed only at 6 and 12 months after diagnosis, respectively. In this series of patients, PBDC1 and PBDC2 numbers inversely correlated with VEGF serum levels (p < 0.001), suggesting a possible effect of this cytokine on DC compartment. In culture, the exposure of monocyte-derived DC to VEGF produced a dramatic alteration of DC differentiation by (1) induction of apoptosis, (2) alteration of DC immunophenotypic profile and (3) increased CXCR4 expression. Exposure to anti-VEGF blocking antibodies reversed VEGF inhibitory effects in all cases.

Conclusions: These findings suggest that in colorectal cancer patients there is a numerical and functional impairment of PBDC compartment possibly related to the stage of the disease and to VEGF levels.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism
  • Apoptosis
  • Case-Control Studies
  • Cell Count
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / surgery
  • Dendritic Cells*
  • Female
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prospective Studies
  • Vascular Endothelial Growth Factor A / metabolism*


  • Antigens, CD
  • Vascular Endothelial Growth Factor A