肥大细胞膜蛋白在胃癌发生发展中的作用及其病理学意义
The Role of Mast Cell Membrane Proteins in the Occurrence and Development of Gastric Cancer and Their Pathological Significance
DOI: 10.12677/acm.2026.1693200, PDF,    科研立项经费支持
作者: 农祖霖：右江民族医学院附属医院临床病理诊断与研究中心，广西 百色；广西肝胆疾病分子病理学重点实验室，广西 百色；右江民族医学院临床医学院，广西 百色；蒋 旗：右江民族医学院附属医院消化内科，广西 百色；黄圆叶, 詹雨平, 何欣欣, 胡 渝, 苏群英：右江民族医学院附属医院临床病理诊断与研究中心，广西 百色；广西肝胆疾病分子病理学重点实验室，广西 百色
关键词: 胃癌；肥大细胞；膜蛋白；c-KIT；CXCR4；PD-L1；ST2；肿瘤微环境；Gastric Cancer； Mast Cell； Membrane Proteins； c-KIT； CXCR4； PD-L1； ST2； Tumor Microenvironment
摘要: 肥大细胞(mast cell, MC)是胃黏膜固有免疫与组织稳态的重要效应细胞，在胃癌(gastric cancer, GC)微环境中呈现高度可塑性：既可通过释放蛋白酶、血管生成因子与脂质介质促进肿瘤生长、血管/淋巴管生成及转移，也可在特定条件下参与抗肿瘤免疫。近年来，围绕“肥大细胞表达的膜蛋白”展开的研究提示：MC并非单纯的旁观者，其在GC中可通过一系列膜受体/共刺激或免疫检查点分子实现募集–激活–免疫调控–组织重塑的级联放大，从而影响肿瘤进展与治疗反应。其中，c-KIT (CD117)/SCF轴决定MC生存与功能状态；CXCR4介导其向肿瘤组织定向迁移；PD-L1、PD-1等免疫检查点分子使MC获得免疫抑制表型并削弱T细胞效应；IL-33受体ST2 (IL1RL1)驱动MC与巨噬细胞、Treg等的互作并促进肿瘤发展；FcεRI与MRGPRX2等激活受体为MC去颗粒与介质释放提供触发机制；Siglec-8等抑制性受体则为“功能刹车”与治疗干预提供新靶点。本文聚焦GC背景下MC膜蛋白的表达谱、机制证据、病理检测要点及转化治疗策略，旨在为肿瘤免疫微环境分层评估与新型联合治疗提供病理学视角。GC中“肿瘤内肥大细胞经CXCL12-CXCR4募集并在TNF-α驱动下上调PD-L1抑制T细胞”及“IL-33/ST2介导肥大细胞激活促进肿瘤进展”等关键通路，为该领域奠定了机制框。
Abstract: Mast cells (MCs) are key innate immune and tissue-homeostatic effector cells in the gastric mucosa. In gastric cancer (GC), MCs exhibit pronounced plasticity and can promote tumor growth, angiogenesis/lymphangiogenesis, invasion and immune evasion through the release of proteases, cytokines and lipid mediators, while context-dependent anti-tumor functions have also been reported. Emerging evidence highlights that MC membrane proteins orchestrate a recruitment-activation-immune modulation-tissue remodeling cascade in the GC tumor microenvironment (TME). The c-KIT/SCF axis governs MC survival and functional programs; CXCR4 directs MC chemotaxis toward tumors; immune checkpoint molecules such as PD-L1/PD-1 endow MCs with immunosuppressive phenotypes; ST2 (IL1RL1), the receptor for IL-33, promotes MC activation and cross-talk with macrophages and regulatory T cells; FcεRI and MRGPRX2 provide major activation routes for degranulation; inhibitory receptors such as Siglec-8 may serve as potential therapeutic brakes. This review summarizes GC-focused advances in MC membrane proteins, discusses pathological assessment and translational opportunities, and proposes future directions for TME stratification and combinational therapies. Mechanistically, tumor-recruited MCs via the CXCL12-CXCR4 axis upregulate PD-L1 under TNF-α signaling to suppress T cells, and IL-33/ST2-driven MC activation promotes GC progression.
文章引用：农祖霖, 蒋旗, 黄圆叶, 詹雨平, 何欣欣, 胡渝, 苏群英. 肥大细胞膜蛋白在胃癌发生发展中的作用及其病理学意义[J]. 临床医学进展, 2026, 16(9): 1597-1604. https://doi.org/10.12677/acm.2026.1693200

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