Abstract
Immune checkpoint inhibitors are a promising therapy for the treatment of cancers, including melanoma, that improved benefit clinical outcomes. However, a subset of melanoma patients do not respond or acquire resistance to immunotherapy, which limits their clinical applicability. Recent studies have explored the reasons related to the resistance of melanoma to immune checkpoint inhibitors. Of note, miRNAs are the regulators of not only cancer progression but also of the response between cancer cells and immune cells. Investigation of miRNA functions within the tumor microenvironment have suggested that miRNAs could be considered as key partners in immunotherapy. Here, we reviewed the known mechanism by which melanoma induces resistance to immunotherapy and the role of miRNAs in immune responses and the microenvironment.
Highlights
Melanoma is the major skin cancer-related cause of death
The results demonstrated that deletion of chromosome 15q, including B2M, caused loss of phosphatase and tensin homolog (PTEN) and cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous deletion was observed in the resistance to immunotherapy in melanoma patients [30]
Immunotherapy has the ability to prolong the survival of melanoma patients, resistance is a limitation
Summary
Melanoma is the major skin cancer-related cause of death. The survival rate of metastatic melanoma is approximately 10–15%, even though many effective approaches, such as targeted therapy and immunotherapy, have gained the approval by the Food and Drug. Immunotherapy has improved the clinical outcomes, approximately 50% of melanoma patients do not respond or acquire resistance to immune checkpoint inhibitors [8,12]. Immunosuppressive tumor microenvironment-regulated miRNAs are related to overall survival in melanoma patients [14]. A clinical trial of cobomarsen, an inhibitor of miR-155 (NCT02580552), has been designed to treat patients diagnosed with cutaneous T-cell lymphoma, chronic lymphocytic leukemia, diffuse large B-cell lymphoma, or adult T-cell leukemia/lymphoma These findings indicated that miRNAs play a central role in tumor progression and the tumor microenvironment. We discuss the resistance mechanism of melanoma to immunotherapy and the involvement of miRNAs in the response to immune checkpoint inhibitors and the tumor microenvironment
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