AUTHOR=Liang Yiwen , Zheng Yan , Zeng Yuyan , Hu Chengjing , Si Yuqi , Fan Xiqian , Chen Qihua 

TITLE=Immune checkpoint inhibitors in melanoma: mechanisms, immune cell interactions, and the tumour microenvironment

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1691608

DOI=10.3389/fimmu.2025.1691608

ISSN=1664-3224

ABSTRACT=Melanoma is a highly aggressive and metastatic malignant tumor originating from melanocytes, with globally rising incidence rates that pose significant challenges to patient prognosis. Traditional therapies for advanced melanoma have limited efficacy. In recent years, the emergence of immune checkpoint inhibitors (ICIs) has significantly altered this landscape by reactivating the body’s antitumor immune response through blocking interactions between immune checkpoint proteins and their ligands, demonstrating remarkable therapeutic outcomes. However, some patients do not respond to ICIs or develop resistance, indicating that treatment responses involve complex interactions between tumors, immune cells, and the tumor microenvironment. This review comprehensively summarizes the mechanisms of ICIs, delves into the roles of various immune cells (including T cells, NK cells, macrophages, T helper cells, dendritic cells, and B cells) and the tumor microenvironment (TME), and explores their impact on ICI efficacy. It further distinguishes the application of ICBs across different disease stages (primary, adjuvant, neoadjuvant, and metastatic) and highlights the role of skin-specific immune cells (e.g., TRM, Langerhans cells) and microenvironmental components (e.g., skin microbiome). This review focuses on the mechanisms of ICIs in melanoma therapy, exploring the interactions between immune cells and the skin microenvironment in melanoma development and their impact on ICI efficacy. It aims to provide new insights and theoretical foundations for optimizing immunotherapy strategies in melanoma treatment.