CD4 and melanoma: Similarly, knocking down Per1/2 in mice (Per1/2-/-mice) increased the efficacy of cisplatin in reducing melanoma tumor growth rate at both low and high doses, and this effect could be attributed to activation of immune response mediated by CD4+ and CD8+ T cell populations, which clearly demonstrates that circadian clock genes, specifically PER2, affects the immune response to melanoma tumors [54].