Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions

Abstract

Melanoma is one of the most immunologic malignancies based on its higher prevalence in immune-compromised patients, the evidence of brisk lymphocytic infiltrates in both primary tumors and metastases, the documented recognition of melanoma antigens by tumor-infiltrating T lymphocytes and, most important, evidence that melanoma responds to immunotherapy. The use of immunotherapy in the treatment of metastatic melanoma is a relatively late discovery for this malignancy. Recent studies have shown a significantly higher success rate with combination of immunotherapy and chemotherapy, radiotherapy, or targeted molecular therapy. Immunotherapy is associated to a panel of dysimmune toxicities called immune-related adverse events that can affect one or more organs and may limit its use. Future directions in the treatment of metastatic melanoma include immunotherapy with anti-PD1 antibodies or targeted therapy with BRAF and MEK inhibitors.

Figure 1

Global incidence of Melanoma of skin. From Matthews NH et al. “Epidemiology of Melanoma” Cutaneous Melanoma: Etiology and Therapy. 2017 [26].

Figure 2

Suggested mechanisms of immunoediting in melanoma of unknown primary. From Gyorki et al., The delicate balance of melanoma immunotherapy. Clinical & Translational Immunology 2013 [34].

Figure 3

Principle of adoptive cell therapy. From Halama et al., Advanced Malignant Melanoma: Immunologic and Multimodal Therapeutic Strategies. J Oncol. 2010 [73].