胃癌免疫微环境的基础理论与临床转化研究 进展

Research Advances in Basic Theory and Clinical Translation of the Gastric Cancer Immune Microenvironment

摘要: 胃癌作为全球范围内发病率和死亡率均居前列的恶性肿瘤，其发生发展与肿瘤免疫微环境(Tumor Immune Microenvironment, TIME)的动态调控密切相关。TIME由免疫细胞、基质细胞、细胞因子及胞外基质等共同构成，通过复杂的细胞间相互作用参与肿瘤的免疫逃逸、侵袭转移及治疗抵抗。近年来，随着免疫检查点抑制剂等免疫治疗策略的临床应用，TIME的异质性、分子机制及临床转化价值成为研究热点。本综述系统梳理了胃癌TIME的组成特征、作用机制及异质性研究进展，深入分析其流行病学特征、病理机制及诊断技术，并探讨靶向TIME的治疗策略与临床转化挑战。研究表明，胃癌TIME中免疫细胞的功能状态、细胞因子网络的失衡及免疫逃逸机制的激活是影响患者预后和治疗响应的关键因素。基于TIME特征的个性化治疗方案(如免疫检查点抑制剂联合靶向治疗)已展现出初步疗效，但仍面临异质性、技术瓶颈等挑战。未来需通过多组学技术整合、动态监测模型构建及新型靶点开发，推动胃癌免疫治疗的精准化与个体化。

Abstract: Gastric cancer, a malignancy with high global incidence and mortality, is closely linked to the dynamic regulation of the tumor immune microenvironment (TIME). The TIME is composed of immune cells, stromal cells, cytokines, and the extracellular matrix, which collectively mediate complex intercellular interactions involved in tumor immune evasion, invasion, metastasis, and therapy resistance. In recent years, with the clinical application of immunotherapy strategies such as immune checkpoint inhibitors, the heterogeneity, molecular mechanisms, and clinical translational significance of the TIME have become major research focuses. This review systematically outlines the compositional characteristics, functional mechanisms, and recent advances in understanding the heterogeneity of the TIME in gastric cancer. It provides an in-depth analysis of its epidemiological features, pathological mechanisms, and diagnostic technologies, and discusses therapeutic strategies targeting the TIME along with challenges in clinical translation. Studies have shown that the functional status of immune cells, the imbalance in cytokine networks, and the activation of immune escape mechanisms within the gastric cancer TIME are key factors influencing patient prognosis and treatment response. Personalized treatment strategies based on TIME features, such as combining immune checkpoint inhibitors with targeted therapies, have demonstrated preliminary efficacy but still face challenges like heterogeneity and technological limitations. Future efforts should focus on integrating multi-omics technologies, constructing dynamic monitoring models, and developing novel therapeutic targets to advance precision and personalized immunotherapy for gastric cancer.