The CD4+ T-cells produce IL-2, IFN-γ and TNF-α to create an inflammatory micro-environment, favoring the activity of the infiltrating cytotoxic CD8+ T-cells (CTLs), thereby contributing to the elimination of the tumor.50 This indirect mechanism of action must be behind the success of adoptive transfer of ex vivo expanded tumor-specific CD4+ T-cells in promoting clinical remission of melanoma 51 and cholangiocarcinoma.52 A tumor expressing functional MHC-II molecules could potentially amplify the ongoing immune response, thus contributing to a more effective clearance of the tumor. This evidence concerns the gene CD8A and melanoma.