Abnormally enhanced blood concentrations of vascular endothelial growth factor (VEGF) in metastatic cancer patients and their relation to circulatingdendritic cells, IL-12 and endothelin-1

Elevated VEGF blood concentrations have been proven to be associated with p oor prognosis in human neoplasms. This finding is generally explained as a consequence of the potential angiogenic properties of VEGF itself. However, preliminary experimental studies suggest that VEGF, in addition to its ang iogenic activity, may also play an immunosuppressant role by inhibiting den dritic cell (DC) maturation. The present study was performed to analyze blo od levels of VEGF in cancer patients in relation to those of another potent ially angiogenic tumor growth factor, endothelin-1 (ET-1), and to the absol ute number of circulating immature and mature DC, and serum levels of the b est known antitumor cytokine, IL-12. The study was performed in 100 healthy controls and in 80 solid tumor patients (colorectal cancer: 24; gastric ca ncer: 17; cancer of pancreas: 4; lung cancer. 13; breast cancer: 11; renal cell cancer: 6; gynecologic tumors: 5), 48 of whom showed distant organ met astases. In each patient, we have evaluated serum concentrations of VEGF-16 5, total VEGF, ET-1, IL-12 and the circulating number of immature (CD123(+) ) and mature (CD11c(+)) DC. Mean serum levels of VEGF-165 were significantl y higher in metastatic patients than in controls or in non-metastatic patie nts, whereas the total amounts of VEGF were not significantly higher. Moreo ver, it has been observed that patients with abnormally elevated blood conc entrations of VEGF-165 showed significantly lower mean values of immature D C, mature DC and IL-12 and significantly higher mean levels of ET-1 than th ose with normal concentrations. This study, by confirming that advanced neo plastic disease may be associated with increased endogenous secretion of VE GF, seems to suggest that the association between high blood levels of VEGF and poor prognosis in cancer does not depend only on VEGF-induced stimulat ion of the neovascularization, but also on VEGF-related immunosuppression.