CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
GPI 锚定的 LY6/uPAR 家族蛋白在连接膜微区与免疫调节及疾病中的作用
英文原题：The role of GPI-anchored LY6/uPAR family proteins in connecting membrane microdomains with immune regulation and diseases.
查看英文原题
The role of GPI-anchored LY6/uPAR family proteins in connecting membrane microdomains with immune regulation and diseases.
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中文摘要
糖基磷脂酰肌醇（GPI）锚定的LY6/uPAR家族蛋白结构保守，但在免疫信号调控方面功能多样。该家族成员具有特征性的三指LY6/uPAR（LU）结构域，优先定位于脂筏；成员包括LY6A、LY6C、LY6E、LY6G、CD59、PSCA和uPAR，可调控T细胞和B细胞活化、树突状细胞成熟、中性粒细胞和自然杀伤（NK）细胞应答以及巨噬细胞极化等重要免疫过程。越来越多研究发现，这些蛋白参与癌症、感染性疾病、自身免疫性疾病和神经炎症的发病机制。GPI锚定有助于受体预先定向、形成纳米簇，并在膜微区内快速转导信号，从而使免疫信号得到精准的时空调控。多个LY6/uPAR家族成员已成为有前景的临床靶点，转化策略包括CAR-T 细胞疗法、抗体药物偶联物及脂筏调节剂。本综述全面概述当前认识，将LY6/uPAR蛋白的结构、空间分布和功能特征与其在健康及疾病中的意义联系起来，指出尚待解决的关键机制问题，并强调精准免疫学领域新兴的转化机会。
展开英文摘要原文
Glycosylphosphatidylinositol (GPI)-anchored LY6/uPAR family proteins are structurally conserved yet functionally diverse regulators of immune signaling. Defined by a characteristic three-finger LY6/uPAR (LU) domain and preferential localization to lipid rafts, members such as LY6A, LY6C, LY6E, LY6G, CD59, PSCA, and uPAR orchestrate essential immune processes, including T and B cell activation, dendritic cell maturation, neutrophil and natural killer (NK) cell responses, and macrophage polarization. These proteins are increasingly implicated in the pathogenesis of cancer, infectious diseases, autoimmune disorders, and neuroinflammation.
GPI anchoring facilitates receptor pre-orientation, nanocluster formation, and rapid signal transduction within membrane microdomains, thereby enabling precise spatial and temporal control of immune signaling. Several LY6/uPAR members have emerged as promising clinical targets, with translational strategies encompassing CAR-T cell therapies, antibody-drug conjugates, and lipid raft-modulating agents.
This review presents a comprehensive overview of current knowledge, linking the structural, spatial, and functional characteristics of LY6/uPAR proteins to their relevance in health and disease, identifying key unresolved mechanistic questions, and underscoring emerging translational opportunities within the context of precision immunology.
论文信息
- 作者
- Wen J、Wu L、Zhong S、Shan H、Luo JL
- 第一作者单位
- The Cancer Research Institute and the Second Affiliated Hospital, Hengyang Medical School, University of South China (USC), Hunan 421001, China; MOE Key Lab of Rare Pediatric Diseases, Hengyang Medical School, USC, Hunan 421001, China.China
- 通讯作者单位
- The Cancer Research Institute and the Second Affiliated Hospital, Hengyang Medical School, University of South China (USC), Hunan 421001, China; MOE Key Lab of Rare Pediatric Diseases, Hengyang Medical School, USC, Hunan 421001, China; Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, USC, Hunan 421001, China; National Health Commission Key Laboratory of Birth Defect Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, USC, Hunan 410008, China. Electronic address: jlluo@usc.edu.cn.China
- 文献类型
- 综述
- 期刊
- Critical reviews in oncology/hematology2025 Dec
- 原文标识
- PubMed 41016505 · DOI 10.1016/j.critrevonc.2025.104971