CD4 and melanoma: The first set of analyses demonstrated a generally impaired function of the adaptive immune system: The expression of the CD3ζ chain on CD4+ and CD8+ T cells as well as the frequency of IFNγ-secreting CD4+ and CD8+ T cells in response to stimulation with PMA and ionomycin in stage IV melanoma patients were significantly reduced compared to healthy donors suggesting a state of immune exhaustion, which is well established in settings of continued antigen-stimulation of T cells such as chronic infections, autoimmune diseases and advanced cancer [20].