Immunotherapy in Melanoma: Recent Advances and Future Directions

Abstract

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.

Can we yet use tertiary lymphoid structures as predictive biomarkers for immunotherapy response in melanoma?

“…The onset of immunotherapy has markedly transformed the treatment strategy for melanoma, bringing about a notable shift in both early and advanced stages of the cancer. Specifically, immune checkpoint inhibitors (ICIs) have shown remarkable effectiveness in this context [20]. Ipilimumab, the first ICI, was authorized by the FDA in 2011 for the treatment of unresectable or metastatic melanoma and demonstrated superior efficacy over chemotherapy [21].…”

“…With the approval of ICIs, there has been a transformative impact on the treatment outcomes of malignancies that were once considered incurable with limited therapeutic choices, particularly in the case of advanced or metastatic cancers [20]. Furthermore, immunotherapy has opened up the prospect of establishing long-term protection against cancer recurrence by fostering immunological memory.…”

Exploring the landscape of drug resistance in gastrointestinal cancer immunotherapy: A review

“…Its range of therapies includes immune checkpoint inhibitors (ICIs), cancer vaccines, and the innovative method of adoptive cell transfer (ACT). [5][6][7] These treatments have yielded promising outcomes in various cancers, such as lung cancer, [8,9] breast cancer, [10] and melanoma, [11,12] resulting in sustained responses and enhanced survival for some patients. However, the effectiveness of immunotherapy for GI cancers has not been as pronounced, especially when compared to its notable successes in treating cancers like melanoma and lung cancer.…”

BCKDHA contributes to melanoma progression by promoting the expressions of lipogenic enzymes FASN and ACLY

“…[1][2][3] Thus, accumulative attention has been paid to the establishment of therapeutic approaches intervening in the above aspects of melanoma biology. 4 In the past few decades, due to the revolutionary advances in the development of targeted therapy and immunotherapy, 5,6 the prognosis of patients with melanomas have gained unprecedented progress. 7,8 Nevertheless, the 5-year survival of those with metastasis remains far from satisfaction, mainly resulting from low response rate and the inevitable occurrence of treatment resistance to current available therapeutic methods.…”