Human uveal melanoma cells inhibit the immunostimulatory function of dendritic cells

Abstract

Dendritic cells are critical for the induction of anti-tumor immunity. Recent studies suggest that some tumors may avoid immune destruction by inhibiting dendritic cell function. In this study, we investigated the effects of uveal melanoma on human dendritic cell phenotype and functions including surface antigen expression, cytokine production, and T cell activation. Dendritic cells were generated in the presence of GM-CSF and IL-4 from peripheral blood mononuclear cells of healthy donors. On day 5 of culture, dendritic cells were co-cultured with human uveal melanoma cells for 24 h, and then purified using magnetic beads. The maturation of dendritic cells was induced by TNF-α and the phenotype of dendritic cells was analyzed by flow cytometry. The expression of dendritic cell markers and antigen presenting cell markers decreased when dendritic cells were co-cultured with uveal melanoma cells. Moreover, co-culture with uveal melanoma cells led to apoptosis of dendritic cells as shown by 1.5-fold increase in surface phosphatidylserine. Also, dendritic cells co-cultured with uveal melanoma showed diminished ability to produce IL-12 and IL-10. Finally, dendritic cells co-cultured with uveal melanoma inhibited the proliferation of allogeneic T cells in mixed lymphocyte reaction. These findings suggest a mechanism by which uveal melanoma escape immune destruction and have significant implications for tumor-pulsed dendritic cell vaccines for the treatment of uveal melanoma.