Ma Yiqun, Zhang Lin, Liu Weimin
Department of Burns and Plastic Surgery, Kunming Children's Hospital, Children's Hospital Affiliated to Kunming Medical University, Kunming, China.
Department of Orthopaedic, The Third Affiliated Hospital of Shenzhen University (Luohu People's Hospital), Shenzhen, China.
Front Immunol. 2025 Aug 27;16:1608215. doi: 10.3389/fimmu.2025.1608215. eCollection 2025.
Melanoma frequently develops bone metastases, leading to skeletal-related events and poor survival. The tumor microenvironment (TME) plays a pivotal role in melanoma progression, bone metastasis, and immunotherapy resistance. Key immunosuppressive cells including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T cells (Tregs), and cancer-associated fibroblasts (CAFs) promote immune evasion and osteolytic bone destruction via RANKL-dependent and -independent mechanisms. Immune checkpoint inhibitors (ICIs), including anti-CTLA-4 and anti-PD-1/PD-L1 therapies, have revolutionized melanoma treatment, yet resistance remains common due to TME immunosuppression. Emerging strategies, such as combination therapies, aim to enhance efficacy by reshaping the TME. This review synthesizes current knowledge on TME-driven immunosuppression, bone metastasis mechanisms, and immunotherapeutic advancements, offering insights into overcoming resistance and improving patient outcomes.
黑色素瘤常发生骨转移，导致骨相关事件并影响生存率。肿瘤微环境（TME）在黑色素瘤进展、骨转移和免疫治疗耐药中起关键作用。关键的免疫抑制细胞，包括髓源性抑制细胞（MDSC）、肿瘤相关巨噬细胞（TAM）、调节性T细胞（Treg）和癌症相关成纤维细胞（CAF），通过RANKL依赖性和非依赖性机制促进免疫逃逸和溶骨性骨破坏。免疫检查点抑制剂（ICI），包括抗CTLA-4和抗PD-1/PD-L1疗法，彻底改变了黑色素瘤的治疗方式，但由于TME免疫抑制，耐药现象仍然普遍。新兴策略，如联合疗法，旨在通过重塑TME提高疗效。本综述综合了当前关于TME驱动的免疫抑制、骨转移机制和免疫治疗进展的知识，为克服耐药性和改善患者预后提供见解。
