中国癌症杂志2026，Vol.36Issue(8)：755-762,8.DOI:10.19401/j.cnki.1007-3639.2026.08.004
Siglec-15介导肿瘤免疫逃逸的机制与靶向治疗进展及展望
Mechanisms of tumor immune escape mediated by Siglec-15 and advances and prospects in targeted therapy
摘要
Abstract
Immune checkpoint blockade targeting the programmed cell death protein-1(PD-1)and its ligand PD-L1 has revolutionized cancer immunotherapy;however,a substantial proportion of patients exhibit primary or acquired resistance,underscoring the existence of PD-1 independent immunosuppressive pathways within the tumor microenvironment.In this context,Sialic acid-binding immunoglobulin-type lectin 15(Siglec-15)has emerged as a distinct immune checkpoint molecule operating independently of the canonical PD-1/PD-L1 axis and has garnered increasing attention in tumor immunology.Siglec-15 is preferentially expressed in multiple solid tumors and tumor-associated myeloid populations,with a spatial expression pattern that is often complementary to that of PD-L1.Functionally,Siglec-15 modulates immune synapse signaling between myeloid cells and effector T lymphocytes,leading to impaired T cell activation,proliferation,and cytokine production,thereby contributing to immune evasion within the tumor microenvironment.Accumulating evidence indicates that Siglec-15 mediated immunosuppression represents a mechanistically distinct pathway that may account,at least in part,for resistance to current immune checkpoint inhibitors.A comprehensive understanding of the structural features of Siglec-15,its regulatory networks,and its context-dependent immunological functions is therefore essential.Elucidating these mechanisms will not only deepen insights into the complexity of tumor immune regulation but also facilitate the rational development of next-generation immunotherapeutic strategies aimed at overcoming resistance to existing checkpoint blockade therapies.关键词
Siglec-15/免疫检查点抑制剂/肿瘤微环境/靶向治疗/免疫治疗/免疫逃逸Key words
Siglec-15/Immune checkpoint inhibitor/Tumor microenvironment/Targeted therapy/Immunotherapy/Immune escape分类
医药卫生引用本文复制引用
王诗惠,郑天清..Siglec-15介导肿瘤免疫逃逸的机制与靶向治疗进展及展望[J].中国癌症杂志,2026,36(8):755-762,8.基金项目
国家自然科学基金(22277109). National Natural Science Foundation of China(22277109). （22277109）
