Current and Emerging Perspectives on Immunotherapy for Melanoma

Novel immunotherapeutic treatments are aimed at reversing the action of inhibitory pathways that restrain the T-cell-dominated immune-mediated defense against cancer. The first immune-inhibitory protein to be discovered was cytotoxic T-lymphocyte antigen-4 (CTLA-4). The effectiveness of a CTLA-targeted antibody in treating melanoma was an impetus for the use of programmed cell death-1 (PD-1) inhibitors in cancer treatment. Important differences between the use of CTLA-4 inhibitors and PD-1 inhibitors in treatment include the patterns of expression of each receptor and its ligands and sites of action, as CTLA-4 blockade has been noted to provide more global effects, whereas those of PD-1 inhibition are observed at the tumor site. Although each treatment has been associated with impressive benefits in advanced melanoma, recent comparative studies suggest that PD-1 inhibitors may be more effective than CTLA-4 inhibition and that the most optimal results may be observed using both agents in those who can tolerate the increased toxicity that accompanies combination treatment. The most common adverse reactions include skin effects using either CTLA-4-blocking antibody or PD-1 inhibitors, colitis using CTLA-4 blockade, or thyroid disease using PD-1 inhibitors.