The use of
immunotherapy in the treatment of advanced and high-risk
melanoma has led to a striking improvement in outcomes. Although the incidence of
melanoma has continued to rise, median survival has improved from approximately 6 months to nearly 6 years for patients with advanced inoperable stage IV disease. Recent understanding of the tumor microenvironment and its interplay with the immune system has led to the
explosive development of novel
immunotherapy treatments. Since the approval of the therapeutic
cytokines interleukin-2 and
interferon alfa-2 in the 1990s, the development of novel
immune checkpoint inhibitors (ICIs),
oncolytic virus therapy, and modulators of the tumor microenvironment have given way to a new era in
melanoma treatment.
Monoclonal antibodies directed at
programmed cell death protein 1 receptor (PD-1) and its
ligand (PDL-1), cytotoxic T-lymphocyte-associated
protein 4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3) have provided robust activation of the adaptive immune system, restoring immune surveillance leading to host
tumor recognition and destruction. Multiple other immunomodulatory
therapeutics are under investigation to overcome resistance to ICI
therapy, including the toll-like receptor-9 (TLR-9) and 7/8 (TLR-7/8) agonists, stimulator of
interferon genes (
STING) agonists, and
fecal microbiota transplantation. In this review, we focus on the recent advances in
immunotherapy for the treatment of
melanoma and provide an update on novel
therapies currently under investigation.