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释放潜能:胃癌免疫治疗的当前格局与未来方向

英文原题:Unlocking the potential: current landscape and future directions of immunotherapy in gastric cancer.

PubMed 2026/05/12(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

胃癌(GC)是全球癌症相关死亡的第三大原因,其治疗仍十分棘手。

中文摘要

胃癌(GC)是全球癌症相关死亡的第三大原因,其管理仍极具挑战。免疫治疗因疗效显著且毒性可接受而备受关注,其发展速度已超过传统疗法。然而,分子异质性和免疫抑制性肿瘤免疫微环境(TIME)阻碍了相当一部分患者的治疗应答。本综述总结最新治疗进展,包括免疫检查点抑制剂(ICI)、过继细胞治疗(ACT)、单克隆抗体和抗体药物偶联物(ADC)、癌症疫苗、TIL(肿瘤浸润淋巴细胞)疗法及CAR-T细胞疗法。RNA干扰纳米递送系统、免疫佐剂和微生物群调节等新兴策略不断发展,旨在将“冷”肿瘤转化为“热”肿瘤。主要挑战仍包括原发性耐药、免疫相关不良事件(irAE)和抗原异质性,凸显了精细患者分层的必要性。PD-L1表达、肿瘤突变负荷(TMB)、错配修复状态、EB病毒(EBV)阳性和循环肿瘤DNA(ctDNA)等经典生物标志物均具有预测价值,但仍受空间异质性和时间动态变化限制。因此,我们重点介绍整合代谢、表观遗传和细胞死亡特征的新兴生物标志物,为精准免疫治疗和持续优化GC治疗算法提供路线图。

展开英文摘要原文

Gastric cancer (GC) ranks as the third leading cause of cancer-related mortality worldwide, and its management remains formidable. Immunotherapy has been highly praised for its remarkable efficacy and acceptable toxicity, and its development has outpaced that of traditional therapies. However, molecular heterogeneity and the immunosuppressive tumor immune microenvironment (TIME) have hindered the treatment response of a considerable number of patients. This review synthesizes the latest therapeutic advances, spanning immune-checkpoint inhibitors (ICIs), adoptive cell therapy (ACT), monoclonal antibodies and antibody drug conjugates (ADCs), cancer vaccines, tumor-infiltrating lymphocyte (TIL) therapy, and CAR-T cells therapy. Emerging strategies such as RNA interference nano-delivery systems, immune adjuvants, and microbiota modulation are constantly evolving to transform "cold" tumors into "hot" tumors. Persistent challenges include primary resistance, immune-related adverse events (irAEs) and antigenic heterogeneity, underscoring the imperative for refined patient stratification. Classical biomarkers such as PD-L1 expression, tumor mutational burden (TMB), mismatch-repair status, Epstein-Barr virus (EBV) positivity and circulating tumor DNA (ctDNA) all demonstrate predictive value but remain constrained by spatial heterogeneity and temporal dynamics. Consequently, we highlight emerging biomarkers that integrate metabolic, epigenetic and cell-death signatures, providing a roadmap for precision immunotherapy and continuous optimization of GC treatment algorithms.

论文信息

作者
Zhou Y、Wei L、Wang L、Zhang B、Liang J
第一作者单位
Department of Clinical Medicine, Qingdao University, Qingdao, China.China
通讯作者单位
Department of Immunology, School of Basic Medicine, Qingdao University, Qingdao, China.China
文献类型
综述
期刊
Frontiers in immunology2026
原文标识
PubMed 42206056 · DOI 10.3389/fimmu.2026.1742723