The approval of immunotherapy for stage II-IV melanoma has underscored the need for improved immune-based predictive and prognostic biomarkers. For resectable stage II-III patients, adjuvant immunotherapy has proven clinical benefit, yet many patients experience significant adverse events and may not require therapy. In the metastatic setting, single agent immunotherapy cures many patients but, in some cases, more intensive combination therapies against specific molecular targets are required. Therefore, the establishment of additional biomarkers to determine a patient’s disease outcome (i.e., prognostic) or response to treatment (i.e., predictive) is of utmost importance. Multiple methods ranging from gene expression profiling of bulk tissue, to spatial transcriptomics of single cells and artificial intelligence-based image analysis have been utilized to better characterize the immune microenvironment in melanoma to provide novel predictive and prognostic biomarkers. In this review, we will highlight the different techniques currently under investigation for the detection of prognostic and predictive immune biomarkers in melanoma.

Introduction: Acral lentiginous melanoma (ALM), a rare subtype, accounts for 2–3% of melanoma cases, primarily affecting the palms, soles, and nail beds and disproportionately affects people of color. This review focuses on clinical insights into ALM and its management, with a focus on race and ethnicity. Methods: A comprehensive literature search was conducted in public databases using the search term “acral melanoma,” and studies focusing on epidemiology, clinical presentation, and treatment outcomes of ALM in various racial and ethnic groups were reviewed. Results: Significant disparities in ALM outcomes exist across racial and ethnic groups, with African, Hispanic, and Asian individuals presenting with thicker, more advanced tumors at diagnosis. These populations encounter unique challenges, including limited access to dermatologic care, under-recognition of melanoma presentation in darker skin types, and socioeconomic barriers leading to delayed diagnosis and treatment. Surgical management may require specialized approaches, such as partial amputation for subungual melanomas. Additionally, there is uncertainty regarding the tumor immune microenvironment (TME) in ALM, with some studies suggesting that it might be less favorable, resulting in a lower response to immunotherapy. Conclusions: ALM affects diverse populations, and the impact of ethnic and racial origin on ALM biology is largely unknown. Addressing disparities in ALM outcomes among racial and ethnic groups is critical for improving patient care. Increased awareness of melanoma risk in individuals with darker skin can significantly impact early detection and treatment. Future research should focus on the genetic and biological factors contributing to morbidity and mortality in ALM patients.

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