Neoadjuvant studies in patients with macroscopic stage III melanoma have been performed using the immunotherapies interferon and ipilimumab. Interferon has no activity in stage IV melanoma, yet there was an objective clinical response in 11 of 17 (55%) patients with stage III melanoma when given neoadjuvantly. Furthermore, 3/17 (15%) had a complete pathological response. Clinical responders had significantly greater increases in endotumoral CD11c and CD3 cells and significantly greater decreases in endotumoral CD83 cells compared with nonresponders. In contrast, ipilimumab confers an overall survival benefit for patients with stage IV melanoma over vaccine or chemotherapy, however the objective response rate is low at 11-15%. In the neoadjuvant study with macroscopic stage III melanoma, pathological responses were not reported, however objective clinical responses were observed in 3/29 (10%) patients. Immune infiltrate cells were noted in most tumours after treatment with ipilimumab, and results correlating biomarker changes with response are awaited.