Role of IL-10 and TGF-β in melanoma

Abstract

IL-10 and TGF-β are immunosuppressive cytokines expressed in tumors including melanoma and, therefore, deemed major cause for failing antitumor immune responses. Re-evaluating their role, we compared their expression by quantitative RT-PCR in melanoma and skin of healthy individuals, tested their induction in dendritic cells and T cells co-cultured with tumor cells, and their effects on the immune cells. Both cytokines as well as their receptors were expressed in melanoma at significantly lower levels than in healthy skin. Consequently, the expressions of IL-10-responsive SOCS-3 and TGF-β-responsive Smad-7 were low in tumors but high in healthy skin. T cells co-cultured with tumor cells developed an anergic state without increased IL-10 or TGF-β expression. In vitro tumor-induced immature dendritic cells produced high IL-10 levels and less efficiently induced T-cell proliferation. Nonetheless, they could be induced to mature, and blocking IL-10 did not alter the capacity of the resulting mature dendritic cells to stimulate T cells. Mature dendritic cells co-cultured with tumor cells produced increased IL-10 but decreased TGF-β and more efficiently induced T-cell proliferation. The lack of correlation of IL-10 and TGF-β with immune deficits in situ and in vitro suggests re-evaluating their roles in cancer.