CD4 and melanoma: In contrast, the combination therapy of melatonin, metformin, and dacarbazine in disseminated melanoma patients, no benefit was observed over dacarbazine monotherapy; however, the increase of CD3+ CD4+ HLA-DR+, CD3+ CD8+ HLA-DR+, CD3+ CD8+, CD4+ CD25high CD127low was observed in patients with clinical benefit [85].