进展期胃癌新辅助免疫治疗的突破与展望

Neoadjuvant immunotherapy for advanced gastric cancer: current advances andfuture prospects

  • 摘要: 本文综述了进展期胃癌新辅助免疫治疗的最新研究进展。通过检索2020-2023年PubMed、Web of Science及中国知网等数据库的相关文献,系统分析了免疫治疗的作用机制、临床应用及生物标志物研究。程序性死亡受体-1(programmed death-1,PD-1)抑制剂联合化疗可显著延长进展期胃癌患者的无进展生存期和总生存期。微卫星不稳定性(microsatellite instability,MSI)、程序性死亡配体-1(programmed death-ligand 1,PD-L1)表达和肿瘤突变负荷(tumor mutational burden,TMB)是重要的预测生物标志物。多组学分析在筛选最佳应答者方面显示出巨大潜力,焦亡相关基因评分系统(pyroptosis-related gene scoring system,PRS)与抗肿瘤免疫浸润呈正相关。肿瘤微环境中的代谢重编程和表观遗传调控在免疫逃逸中发挥关键作用。Claudin 18.2等新兴靶点展现出良好的抗肿瘤活性,联合靶向策略可进一步提高治疗效果。尽管进展期胃癌新辅助免疫治疗已取得显著进展,但仍面临精准筛选适合患者、克服耐药机制等挑战。未来研究应聚焦于验证生物标志物的预测价值,开发个性化治疗策略,深入解析肿瘤微环境动态变化,以及探索新型联合治疗方案以提高临床疗效。

     

    Abstract: This review summarizes recent advances in neoadjuvant immunotherapy for advanced gastric cancer. Through literature search in PubMed, Web of Science, and CNKI databases from 2020 to 2023, we systematically analyzed the mechanisms, clinical applications, and biomarker research. Programmed death-1 (PD-1) inhibitors combined with chemotherapy significantly improve patient outcomes, while microsatellite instability (MSI), programmed death-ligand 1 (PD-L1) expression, and tumor mutational burden (TMB) have been identified as important predictive biomarkers. Multi-omics analysis shows great potential in identifying optimal responders, with pyroptosis-related gene scoring system (PRS) positively correlating with anti-tumor immune infiltration. Metabolic reprogramming and epigenetic regulation in the tumor microenvironment play key roles in immune evasion, while emerging targets such as Claudin 18.2 and combination targeting strategies further enhance therapeutic efficacy. Despite significant progress, precise patient selection and overcoming resistance mechanisms remain major challenges. Future research should focus on biomarker validation, personalized treatment strategy development, tumor microenvironment dynamic analysis, and novel combination therapy exploration to improve clinical outcomes.

     

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