BACKGROUND: Cancer is linked to defects in immunosurveillance. Vaccination studies using dendritic cells (DC) try to re-establish immune responses toward tumor cells. Tumor-derived products such as interleukin-10 (IL-10) have inhibitory effects on DC function, and tumor-bearing hosts exhibit a lower number of DCs, suggesting inhibitory effects of tumor-derived factors on the recruitment of precursor cells. MATERIALS AND METHODS: We generated DCs in the presence and absence of IL-10. DCs were then characterized by flow cytometry and cDNA microarray analysis. RESULTS: IL-10 interferes with differentiation of peripheral blood monocytes to DCs and induces cells with a distinct phenotype. Microarray analysis revealed that IL-10 exhibits inhibitory as well as stimulatory effects on the expression of several genes. Addition of IL-10 to the differentiation cocktail induces a sustained inhibitory effect on subsequent maturation stimuli. CONCLUSION: IL-10 inhibits DC function and redirects differentiation of DCs to cells with a different phenotype, thereby reducing the pool of potential DC precursors.
Biomarkers/metabolism , Cell Differentiation/drug effects , Dendritic Cells/cytology , Gene Expression Profiling , Interleukin-10/pharmacology , Monocytes/cytology , Cells, Cultured , Cytokines/metabolism , Dendritic Cells/drug effects , Dendritic Cells/metabolism , Flow Cytometry , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Interleukin-4/metabolism , Monocytes/drug effects , Monocytes/metabolism , Oligonucleotide Array Sequence Analysis , Phenotype
