Immune checkpoint blockade in melanoma: Advantages, shortcomings and emerging roles of the nanoparticles

The early stages of melanoma could be treated promisingly by surgical resection; however, the challenge is in advanced cases in which targeted therapy could be an option. The expression of immune checkpoints such as CTLA-4, PD-1, PD-L1, TIM-3, LAG-3, and VISTA is at adequate levels in the melanoma tumor microenvironment (TME) implying the promising outcomes of applying immune checkpoint blockades (ICBs). Since the first Food and Drug Administration (FDA) approved ICB, ipilimumab, in melanoma patients, the treatment of melanoma patients with ICBs resulted in improved survival rate and anti-tumor responses, making ICB one of the promising therapeutic approaches. However, due to high biodistribution, these drugs could non-specifically target healthy cells and empower the immune reactions out of control, which results in the incidence of immune-related adverse events. Although there are development management approaches, a new emerging platform is recently available with aid of drug delivery strategies, particularly nanoparticles (NPs). Here, we investigated the recent trials of ICBs in the context of melanoma cases while showing the challenges of this approach. Also, the application of NPs in order to locally deliver ICBs in melanoma tumor models is discussed.