Colorectal Cancer and Tumor Stromal Cells Have Different Effects on the Differentiation and Maturation of Dendritic Cells In Vitro

Abstract

We compared the ability of SW837, SW480, HT-29, Caco-2, and HCT116 colorectal cancer lines and cancer-associated fibroblasts obtained from a colorectal adenocarcinoma biopsy specimen to modulate differentiation and maturation of dendritic cells in co-culture. The expression of surface markers of dendritic cell differentiation (CD1a) and maturation (CD83), as well as the expression of CD14 monocyte marker was evaluated by flow cytometry. Cancer-associated fibroblasts completely suppressed dendritic cell differentiation from peripheral blood monocytes induced by granulocyte-macrophage CSF and IL-4, but had no significant effect on their maturation under the influence of bacterial LPS. On the contrary, tumor cell lines did not interfere with monocyte differentiation, although some of them significantly reduced the level of CD1a expression. In contrast to cancer-associated fibroblasts, tumor cell lines and conditioned medium from primary tumor cell culture suppressed LPS-induced maturation of dendritic cells. These results suggest that tumor cells and cancer-associated fibroblasts can modulate different stages of the antitumor immune response.