During this phase, the malignant melanoma cells interact actively with the immune system; for example, the spontaneous regression of melanoma (20% to 30%) has long been reported, mainly because of strong association between the high heterogeneity of melanoma and the immune response, making it more susceptible to regulation by its own tumor-infiltrating CD4+ T and CD8+ T cells [254–256]. This evidence concerns the gene CD4 and melanoma.