Conversely, high dose cyclophosphamide is lymphodepletive [35,36] and while the use of high dose cyclophosphamide in combination with total body irradiation is critical to increase the effectiveness of adoptive cell therapy (ACT) treatment of melanoma patients [37,38], it is not without associated toxicity and the requirement of CD4 depletion during ACT has been questioned [39]. This evidence concerns the gene CD4 and melanoma.