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

lssue 3, Volume 2
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Small Extracellular Vesicles-Mediated Immunoregulation in Melanoma Progression and Its Implications for Immunotherapy

Xiaodong Li 1,† Wanli Chen 2,† Wanjun Li 2 Jionghan Zhuang 1 Zhongrui Liu 3 Jinheng Wang 1,*

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1
The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China
2
Guangzhou Medical University-Guangzhou Institute of Biomedicine and Health (GMU-GIBH) Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, China
3
The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.

Received: 24 April 2026 Revised: 14 July 2026 Accepted: 13 August 2026 Published: 26 August 2026

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© 2026 The authors. This is an open access article under the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

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Immune Discov. 2026, 2(3), 10007; DOI: 10.70322/immune.2026.10007
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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