胃癌异质性驱动下的肿瘤免疫微环境重塑： 从分子分型到新兴免疫治疗策略的整合进展

Gastric Cancer Heterogeneity-Driven Remodeling of the Tumor Immune Microenvironment: Integrated Advances from Molecular Subtyping to Emerging Immunotherapeutic Strategies

摘要: 胃癌作为一种高度异质性的恶性肿瘤，其发生发展受多因素调控，且在全球范围内具有显著的流行病学差异。近年来，随着分子生物学和免疫学研究的深入，肿瘤免疫微环境(TIME)在胃癌进展、免疫逃逸及治疗响应中的作用日益受到重视。本文系统综述了胃癌的病因学特征与治疗困境，重点探讨了胃癌在细胞组成、分子转录、空间分布及代谢重编程等多个维度上的异质性，及其对TIME重塑和免疫治疗响应的影响。进一步，本文总结了基于免疫特征的胃癌分子分型体系，阐明了不同免疫亚型在预测治疗疗效和指导个体化策略中的临床价值。同时，深入分析了TIME介导的免疫耐受与治疗抵抗机制，并系统梳理了靶向TIME的新兴免疫治疗策略，包括纳米技术、代谢干预、免疫原性细胞死亡诱导及联合治疗等前沿方向。综上，本文旨在为胃癌的精准免疫治疗提供理论基础与临床转化思路。

Abstract: Gastric cancer, as a highly heterogeneous malignant tumor, is regulated by multiple factors and exhibits significant epidemiological differences globally. In recent years, with the advancement of molecular biology and immunology research, the role of the Tumor Immune Microenvironment (TIME) in gastric cancer progression, immune escape, and treatment response has gained increasing attention. This article systematically reviews the etiological characteristics and therapeutic dilemmas of gastric cancer, focusing on its heterogeneity across multiple dimensions, including cellular composition, molecular transcription, spatial distribution, and metabolic reprogramming, as well as its impact on TIME remodeling and immunotherapy response. Furthermore, this review summarizes immune-based molecular classification systems for gastric cancer, elucidating the clinical value of different immune subtypes in predicting treatment efficacy and guiding individualized strategies. Simultaneously, it provides an in-depth analysis of the mechanisms of immune tolerance and therapy resistance mediated by the TIME, and systematically outlines emerging immunotherapeutic strategies targeting the TIME, including nanotechnology, metabolic intervention, induction of immunogenic cell death, and combination therapies. In summary, this article aims to provide a theoretical foundation and clinical translation insights for precision immunotherapy in gastric cancer.