The prognosis for individuals with metastatic melanoma (MM) is not good. Therapeutic strategies to enhance the immune response have some clinical benefit; however, most patients eventually succumb to progressive disease, in part because their immune cells known as dendritic cells (DCs) fail to sustain an effective antitumor T cell immune response. New data generated in vitro using human melanoma cell lines and resected tumors by Norman Sharpless and colleagues at the University of North Carolina School of Medicine, Chapel Hill, has identified one mechanism that represses DC function in MM.