International Immunology, Vol. 13, No. 9, 1147-1154,
September 2001
© 2001 Japanese Society for Immunology
Transforming growth factor-ß produced by progressor tumors inhibits, while IL-10 produced by regressor tumors enhances, Langerhans cell migration from skin
Department of Medicine (Dermatology), Melanoma and Skin Cancer Research, Institute of the University of Sydney at Royal Prince Alfred Hospital, Sydney, NSW 2006, Australia
Correspondence to: G. Halliday
The induction of epidermal immunity depends on activation of local dendritic cells (DC), Langerhans cells (LC), to migrate from the skin to local lymph nodes and mature into potent immunostimulatory cells. We have previously shown that progressor skin tumors, which evade immunological destruction, prevent contact sensitizer-induced LC migration from the skin to draining lymph 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 migration from the skin. Supernatants from two progressor squamous cell carcinoma lines both inhibited LC migration, whereas supernatants from two regressor squamous cell carcinoma lines both enhanced LC mobilization. Transforming growth factor (TGF)-ß1 inhibited, while IL-10 enhanced, LC migration from cultured skin. Both reduced the ability of LC to mature into potent allostimulators. Antibody neutralization identified that TGF-ß1 produced by the progressor tumor was responsible for inhibition of LC migration, while IL-10 produced by the regressor tumor enhanced LC mobilization. Thus these studies show that skin tumors influence DC mobilization from tumors by production of cytokines, and that TGF-ß1 is one factor produced by tumors 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 progressor tumors inhibited, while regressor tumors enhanced DC mobilization.
Keywords: cell trafficking, cytokines, dendritic cells, tumor immunity
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