肿瘤免疫治疗是一种新兴且发展前景广阔的治疗模式。间皮素是一种细胞表面膜蛋白，通过糖基化磷脂酰肌醇锚定 在细胞膜上。间皮素在多种恶性实体肿瘤及血液恶性肿瘤中呈高表达，在少数正常组织的间皮细胞中呈低表达，是一个有潜力 的肿瘤免疫治疗靶点。间皮素的高表达与患者不良预后密切相关，可溶性间皮素已成为多种肿瘤的诊断性生物标志物。应用抗 体药物偶联物和CAR-T细胞治疗等免疫治疗策略，针对间皮素阳性实体瘤进行转化研究并取得了初步进展。本文对间皮素的结 构、体内分布、生物学功能、肿瘤细胞内信号传导机制及其作用、基于核素的靶向成像与治疗策略、抗体偶联药物和CAR-T细胞的 治疗策略，以及面临的挑战进行系统阐述，为进一步探索以间皮素为靶点的免疫治疗提供新思路。

Tumor immunotherapy is an emerging and promising therapeutic modality. Mesothelin, a cell surface membrane protein anchored by glycosylated phosphatidylinositol, is highly expressed in a variety of malignant solid tumors and hematological malignancies, but lowly expressed in the mesothelial cells of a few normal tissues, making it a promising target for tumor immunotherapy. High mesothelin expression is closely associated with poor prognosis patients, and soluble mesothelin has become a diagnostic biomarker for a variety of tumors. Immunotherapeutic strategies, such as antibody-drug conjugates and CAR-T cell therapy, are undergoing translational research for mesothelin-positive solid tumors, achieving preliminary progress. This paper systematically describes the structure, in vivo distribution, biological functions, and intracellular signaling mechanisms of mesothelin in tumor cells. It also covers targeted imaging and therapeutic strategies based on nuclides, antibody-drug conjugates and CAR-T cells, along with the associated challenges. These insights provide a new perspective for further exploration of mesothelin-targeted immunotherapies.

国家自然科学基金面上项目（No. 82272811）