Suppression of the maturation and activation of the dendritic cell line DC2.4 by melanoma-derived factors

Dendritic cells play critical roles in both innate and adaptive immunity, and their numerous functions are tightly linked to their maturation and activation status. Here, we characterize the murine dendritic cell line DC2.4 as a model for studying dendritic cell maturation and activation, and we evaluate the influence of melanoma tumor cells on these processes. Exposure of DC2.4 cells to the Toll-like receptor ligand lipopolysaccharide induces both maturation and activation of these cells, characterized by upregulation of costimulatory molecule expression and proinflammatory cytokine/chemokine production. This maturation and activation is suppressed by soluble factors derived from both the highly tumorigenic B16-F1 and the poorly tumorigenic D5.1G4 murine melanoma cell lines. Interestingly, the extent of DC2.4 immunosuppression by these melanomas correlates with their tumorigenicity, suggesting a potentially vital role for dendritic cell/tumor cell interactions in the regulation of anti-tumor immunity and tumor outgrowth.

► We extensively characterize the phenotype of resting and LPS-stimulated DC2.4 cells.
► We report differential primary/metastatic outgrowth of B16-F1 and D5.1G4 melanomas.
► We demonstrate melanoma-induced suppression of DC2.4 maturation/activation.
► Melanoma-induced suppression of DC2.4 cell activity correlates with tumorigenicity.