Immunotherapy in Acral and Mucosal Melanoma: Current Status and Future Directions

Abstract

Acral and mucosal melanomas are extremely rare in Caucasians; however, they are the predominant melanoma subtypes in Asians and other non-Caucasian populations. Acral and mucosal melanomas share many clinicopathological features, including aggressive phenotypes, similar genetic landscapes, and grim prognoses. In spite of advances in melanoma management, patients with acral and mucosal melanomas show limited benefit from current therapies. The rarity of these subtypes of melanoma is a significant factor contributing to the poor understanding of these pathological subtypes and the lack of effective interventions. Furthermore, the mechanisms contributing to disparities between different types of melanoma remain largely unclear. Herein, we comprehensively review current knowledge on the clinicopathological characteristics and mutational landscapes of acral and mucosal melanomas, as well as providing an overview of current therapies for patients with these aggressive melanoma subtypes, focusing on available immunotherapeutic interventions. We also discuss pathological differences between different melanoma subtypes and summarize current knowledge on melanoma disparities between Asians and Caucasians. Finally, we discuss emerging immunotherapeutic strategies for the treatment of acral and mucosal melanomas, focusing on combination therapies with immune checkpoint inhibitors. Unraveling the unique features of acral and mucosal melanomas is key for their early diagnosis and for the development of effective therapies.

Identification of Three Genes Associated with Metastasis in Melanoma and Construction of a Predictive Model: A Multiracial Identification

“…In Europe and the US, the MM often triggered by ultraviolet and occurred in the skin [ 1 ]. In China, the MM occurred in the mucous except the skin nearly 50% (51.0%, 75/147, in our data) [ 31 ]. Several studies have been reported the useful biomarkers to predict the metastasis in the MM.…”

An Immune-Related Gene Pair Index Predicts Clinical Response and Survival Outcome of Immune Checkpoint Inhibitors in Melanoma

“…Compared with the excellent clinical efficacy of ICI therapy in melanoma, the investigations of its biomarkers are relatively insufficient. The data from the real world revealed that durable responses and favorable long-term outcomes are limited a proportion of melanoma ( 12 ). Thus, more attention should be paid to the discovery and establishment of novel biomarkers for selecting patients who may benefit from ICI therapy.…”

“…With the development of immunotherapy, immune checkpoint inhibitors (ICI) therapy has been approved as the standard treatment for melanoma (4)(5)(6)(7)(8). According to the reports from multiple clinical trials (9)(10)(11)(12), the overall response rate (ORR) of PD-1 blockade with nivolumab or pembrolizumab ranged from 26% to 44%, thus indicating almost 50% of patients with severely progressed melanoma do not obtain complete or partial response, with roughly 24% reach a stable disease only. Notably, as the main subtypes of Asian patients with melanoma, only 10~20% of acral and mucosal cases can benefit from ICI therapy (13)(14)(15).…”

Analyzing Prognostic Hub Genes in the Microenvironment of Cutaneous Melanoma by Computer Integrated Bioinformatics

“…Cutaneous melanoma (CM) is highly malignant, accounting for more than 80% of deaths from skin disease [ 1 , 2 ]. As of late, the incidence and mortality of CM are increasing.…”