Small Extracellular Vesicles-Mediated Immunoregulation in Melanoma Progression and Its Implications for Immunotherapy

Abstract

Melanoma is a highly lethal malignant skin tumor. While immune checkpoint therapy has notably improved patient prognosis, formidable challenges, including drug resistance and immune-related adverse events, remain unresolved. Small extracellular vesicles (sEVs), pivotal mediators of intercellular communication, exert critical roles in melanoma immunoregulation and immune escape. This review focuses on the immunomodulatory effects of sEVs derived from melanoma cells and immune cells (including natural killer cells, macrophages, and dendritic cells) within the tumor immune microenvironment. It further delineates their regulatory mechanisms governing distinct immune cell populations, as well as their intricate associations with immunotherapy resistance. Additionally, the potential of sEVs and their cargo molecules as therapeutic targets and diagnostic biomarkers is explored, offering a theoretical foundation for overcoming immune checkpoint inhibitor resistance and advancing the development of novel melanoma immunotherapies.

Keywords

Melanoma / Small extracellular vesicles / Tumor immune microenvironment / Immunoregulation / Immune escape / Immunotherapy

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