Dendritic cells and vascular endothelial growth factor in colorectal cancer: correlations with clinicobiological findings.
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.
Della Porta
Matteo
M
Section of Hematology, Department of Biomedical Sciences, University of Ferrara, Ferrara, Italy. sse@dns.unife.it
Danova
Marco
M
Rigolin
Gian Matteo
GM
Brugnatelli
Silvia
S
Rovati
Bianca
B
Tronconi
Chiara
C
Fraulini
Chiara
C
Russo Rossi
Antonella
A
Riccardi
Alberto
A
Castoldi
Gianluigi
G
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D016022:Case-Control Studies; D002452:Cell Count; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D003713:Dendritic Cells; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D015703:Antigens, CD; D042461:Vascular Endothelial Growth Factor A