Evidence that activation of the PD-1 and CTLA4 pathways occurs at different stages of T lymphocyte maturation paved the way for combining Ipilimumab and Nivolumab, approved by the FDA in 2015 for unresectable or metastatic melanoma patients, based on the results of the phase III CheckMate 067 trial. Here, PDCD1 is linked to metastatic melanoma.