Elucidation of the resistance mechanisms of immunotherapy by the abnormal signal transduction in melanoma and development of methods to overcome it

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In this study, we have attempted to identify new signaling molecules which trigger multiple immunosuppressive and tumor promoting cytokines and chemokines. By screening dendritic cell(DC) suppressing activity of culture supernatants from the human melanoma cell line treated with human kinase siRNA library, we found 7 kinases. One of them, Serine/Threonine kinase 24(STK24), was found to induce production of IL10, TGF-β, and CCL2 by human melanoma cells. Phosphorylated STK24 was increased in various human melanoma cell lines and melanoma tissue. These results indicate that activated STK24 in cancer cells is involved in the generation of tumor promoting and immunosuppressive tumor microenvironment.