Cancer-related
cytokines may interfere with the differentiation and migration of dendritic cells (DCs) and with the associated up-regulation of co-stimulatory molecules in vitro. We determined whether
cytokines affected the distribution and activation of DCs in patients with
colorectal cancer by measuring the levels of serum
cytokines [
transforming growth factor (TGF)-beta1 and
vascular endothelial growth factor (
VEGF)], DC numbers and phenotype from peripheral blood and mesenteric lymph nodes draining the
cancer, and the infiltration of DCs into
colorectal cancer. A significant increase in the serum level of
TGF-beta1 correlated with a significant reduction in the level of circulating DCs in
cancer patients that was associated with an increased infiltration of Langerhans cells into colorectal mucosa. The prevalence but not intensity of co-stimulatory molecule expression in circulating and mesenteric lymph node DCs was reduced in patients with
colorectal cancer compared to patients with inflammatory bowel conditions. There was no correlation between co-stimulatory molecule expression and serum
TGF-beta1. Thus the circulating DC depletion in
colorectal cancer could be explained by a TGF-beta1-related DC redistribution from the circulation into the
colorectal cancer and adjacent mucosa where DC levels were increased. There was an impairment of DC activation within
colorectal cancer that was not related to serum level of
cytokines.