The Roles of MiRNAs (MicroRNAs) in Melanoma Immunotherapy

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.

MicroRNA-155 and Disease-Related Immunohistochemical Parameters in Cutaneous Melanoma

“…CD8+ T cells have been identified as a critical factor in antitumor activity and are thus a prime candidate for immunotherapy [ 91 ]. Studies have demonstrated that miRNAs can regulate pathways and molecules related to T cells activation [ 92 ], and miR-155 has been recognized as a critical modulator of the immune response [ 93 ], with high expression identified in T/B cells, dendritic cells, and macrophages [ 94 ]. MiR-155 overexpression in CD8+ T cells is linked to an increased antitumor response by reducing the expression of key molecules, such as signal transducer and activator of transcription 5 (STAT5), Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1), Suppressor of cytokine signaling 1 (SOCS1), and Protein Tyrosine Phosphatase Non-Receptor Type 2 (PTPN2) [ 95 ].…”

Non‐coding RNAs in cancer immunotherapy: Predictive biomarkers and targets

“…The level of expression distinguished between patients with metastasis, stage I–II and those with stage III–IV. Interestingly, levels of exosomal miR‐532‐5p and miR‐106b were significantly declined in patients treated with anti‐PD‐1 (pembrolizumab) 52,53 . The study concluded that exosomal miR‐532‐5p and miR‐106b are promising diagnostic and predictive biomarkers for immunotherapy in clinical settings.…”

“…Interestingly, levels of exosomal miR-532-5p and miR-106b were significantly declined in patients treated with anti-PD-1 (pembrolizumab). 52,53 The study concluded that exosomal miR-532-5p and miR-106b are promising diagnostic and predictive biomarkers for immunotherapy in clinical settings. Another study reported that overexpression of miR-1972 and miR-4502 in the serum of melanoma patients treated with anti-PD-1 predicts resistance to anti-PD-1 and development of metastatic melanoma.…”

MSC microvesicles loaded G-quadruplex-enhanced circular single-stranded DNA-9 inhibits tumor growth by targeting MDSCs

“…Suppression of MDSCs is important for improving the immune microenvironment and the treatment of tumors. miRNAs play crucial roles in the regulation of diverse biological processes, including tumorigenesis and inflammation [8,9]. Many studies have been shown that miRNAs regulate MDSCs maturation, differentiation and function [10].…”