More recently, additional effects of the IL28B polymorphism like higher levels of KIR expression on NK cells in non-CC genotype and enhanced caspase activity in CC genotype have been described. To our knowledge this is the first study which analysis the influence of the IL28B polymorphism on the success rate of interferon therapy in a disease other than viral infection. In contrast to the abundant literature showing a clear cut effect of IL28B polymorphism on the therapy-outcome and SVR rates in HCV infected patients, we did not find evidence for a significant association in melanoma Nodakenin patients on adjuvant interferon alpha therapy. The collective presented here is representative of melanoma patients. Several prognostic factors have been identified including tumor thickness, clinical stage but also other factors like e.g. melanin content have been shown to influence treatment response and have been correlated with overall and disease free survival. Thus �C as Mechlorethamine hydrochloride expected – well established risk factors like tumor thickness and clinical stage correlate with disease free and overall survival also in our study population. There may be several explanations for the differing results in HCV and melanoma patients. A recent study showed the correlation of ISG levels and the IL28B polymorphism is inversely correlated in healthy and HCV infected livers. While in healthy livers CC genotype is associated with high mRNA levels of ISG, in the case of HCV infection, patients with the TT genotype show the highest levels of ISG. Thus in the setting of acute or chronic HCV infection the virus seems to induce a shift in the regulation of interferon signaling pathways resulting in a situation where patients with TT genotype already show maximal stimulated ISG levels, that might not be further enhanced by exogenous interferon, i.e. Interferon alpha therapy. This is supported by other studies showing HCV related changes in IFN signaling pathways. Therefore, virally induced changes in the interferon signaling cascade could be a prerequisite to reveal an influence of IL28B polymorphism. Although it is generally accepted that anti-viral and anti-tumor immune responses share common mechanisms, there are also significant differences. Interferons are one of the most important antiviral defense mechanism. Thus, most viruses have developed anti-interferon escape mechanism. Modulation of interferon associated signaling pathways may therefore have much stronger implication for anti-viral than anti-tumor responses masking the effect of IL28B genotype. Furthermore, while anti-viral immune response is directed to non-self, anti-tumor responses must deal with altered self and thus recognize subtle differences between healthy cells and tumors. In addition, tumor epitopes vary much more inter-individually than viral antigens. Also these individual differences could lead to a higher variability of the efficacy interferon treatment, independently of the IL28B polymorphism, making appreciation of its influence more difficult. Our study has certainly several limitations. On one hand we observed only a relatively low number of patients with progressive disease in this cohort. Furthermore, in contrast to HCV infection in melanoma IFN alpha therapy is an adjuvant treatment. While in hepatitis C sustained virologic response defined as absence of HCV-RNA 6 months post treatment can be used as end point, surrogate markers have to be used for melanoma. Thus, due to the natural course of the disease the observation time of this study is short and much longer observation periods might be needed. In conclusion, we did not find any evidence of an association of IL28B polymorphism and treatment success with interferon alpha in patients with melanoma.