CD4 and melanoma: Cancer vaccines inducing antigen-specific CD4+ T cell responses are emerging as promising cancer immunotherapies.2–4 We have studied a vaccine incorporating six intermediate-length peptides that induce CD4+ helper T cell (TH) responses (six helper peptides, 6MHP) and which has clinical activity in patients with advanced melanoma.5–10 The melanoma-associated class II MHC-restricted peptides in the 6MHP vaccine represent melanocytic differentiation proteins and cancer-testis antigens.