CD8A and melanoma: Based on these observations and based on our findings that functional α-MSH/MC-1R signaling up-regulates the expression of cytotoxic genes in CD8+ T cells from melanoma patients (Figure 7B) it is intriguing to speculate that loss of function mutations in MC-1R resulting in a higher incidence of melanoma development or possibly a more severe disease progression might be attributed to a reduced cytolytic function of tumor-specific CD8+ cytotoxic T cells.