Checkpoint inhibitors in the treatment of cutaneous malignant melanoma.

Advanced malignant melanoma has historically been considered a uniformly lethal disease. Recent scientific strides have led to unprecedented understanding of both the molecular alterations and the mechanisms of immune evasion in this malignancy. The realization that an intense and dynamic interplay of stimulatory and inhibitory signals occurs in the "immune synapses" among T cells, tumor cells and dendritic cells, led to the development and subsequent clinical testing of agonist and antagonist monoclonal antibodies (mAb) that can modulate these signals. The resulting positive outcomes of the clinical trials utilizing CTLA-4, PD-1 and PD-L1 modulating drugs, has catapulted the field of immunotherapy into the realm of standard treatment. In this article we review the most important agents and clinical data feeding the ongoing paradigm change in the treatment of advanced melanoma.