Abstract
Melanoma is the most aggressive form of skin cancer, characterized by life-threatening and rapidly spreading progression. Traditional targeted therapy can alleviate tumors by inactivating hyperactive kinases such as BRAF or MEK but inevitably encounters drug resistance. The advent of immunotherapy has revolutionized melanoma treatment and significantly improved the prognosis of melanoma patients. MicroRNAs (miRNAs) are intricately involved in innate and adaptive immunity and are implicated in melanoma immunotherapy. This systematic review describes the roles of miRNAs in regulating the functions of immune cells in skin and melanoma, as well as the involvement of miRNAs in pharmacology including the effect, resistance and immune-related adverse events of checkpoint inhibitors such as PD-1 and CTLA-4 inhibitors, which are used for treating cutaneous, uveal and mucosal melanoma. The expressions and functions of miRNAs in immunotherapy employing tumor-infiltrating lymphocytes and Toll-like receptor 9 agonists are also discussed. The prospect of innovative therapeutic strategies such as the combined administration of miRNAs and immune checkpoint inhibitors and the nanotechnology-based delivery of miRNAs are also provided. A comprehensive understanding of the interplay between miRNAs and immunotherapy is crucial for the discovery of reliable biomarkers and for the development of novel miRNA-based therapeutics against melanoma.