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

Matteo Della Porta, Marco Danova, Gian Matteo Rigolin, Silvia Brugnatelli, Bianca Rovati, Chiara Tronconi, Chiara Fraulini, Antonella Russo Rossi, Alberto Riccardi, Gianluigi Castoldi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)276-284
Number of pages9
JournalOncology
Volume68
Issue number2-3
DOIs
Publication statusPublished - Jul 2005

Keywords

  • Colorectal cancer
  • Dendritic cells
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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