Transforming growth factor-beta produced by progressor tumors inhibits, while IL-10 produced by regressor tumors enhances, Langerhans cell migration from skin

The induction of epidermal immunity depends on activation of local dendriti c cells (DC), Langerhans cells (LC), to migrate from the skin to local lymp h nodes and mature into potent immunostimulatory cells. We have previously shown that progressor skin tumors, which evade immunological destruction, p revent contact sensitizer-induced LC migration from the skin to draining ly mph nodes. In contrast, regressor tumors, which evoke protective immunity, did not inhibit DC mobilization. In this study we utilized the skin explant model to determine the factors produced by skin tumors which regulate LC m igration from the skin. Supernatants from two progressor squamous cell carc inoma lines both inhibited LC migration, whereas supernatants from two regr essor squamous cell carcinoma lines both enhanced LC mobilization. Transfor ming growth factor (TGF)-beta1 inhibited, while IL-10 enhanced, LC migratio n from cultured skin. Both reduced the ability of LC to mature into potent allostimulators. Antibody neutralization identified that TGF-beta1 produced by the progressor tumor was responsible for inhibition of LC migration, wh ile IL-10 produced by the regressor tumor enhanced LC mobilization. Thus th ese studies show that skin tumors influence DC mobilization from tumors by production of cytokines, and that TGF-beta1 is one factor produced by tumor s which can immobilize LC and keep them in an immature form. This is likely to be an important mechanism of tumor escape from the immune system as pro gressor tumors inhibited, while regressor tumors enhanced DC mobilization.