胃癌免疫治疗的现状与前景

Current status and prospects of immunotherapy for gastric cancer

  • 摘要: 近年来,随着对胃癌免疫微环境和免疫逃逸机制认识的加深,免疫治疗正成为治疗体系的重要组成部分。以程序性死亡受体1和(或)程序性死亡受体配体1抑制剂为核心的免疫治疗已由后线拓展至一线及围手术期,其与化疗、靶向和放疗等治疗方式联合,可改善部分患者的缓解率和生存结局。靶向Claudin18.2等抗原的嵌合抗原受体T细胞免疫疗法、肿瘤疫苗及多种免疫调节策略在早期临床研究中亦显示出抗肿瘤活性。然而,目前面临三大核心挑战:耐药机制复杂,涉及肿瘤微环境免疫抑制、调节性T细胞浸润及表观遗传变化;免疫相关不良反应发生率较高,严重者需免疫抑制剂干预;患者异质性导致疗效差异显著,缺乏统一有效的预测标志物。未来发展应聚焦于整合多维度生物标志物,构建精准分层体系,探索免疫治疗与放化疗的最优联合模式,挖掘淋巴细胞活化基因3、T细胞免疫球蛋白黏蛋白分子3、T细胞免疫球蛋白和免疫受体酪氨酸抑制基序结构域蛋白等新型免疫检查点靶点,推动胃癌免疫治疗实现广泛获益与个体化精准治疗目标。笔者系统梳理胃癌免疫治疗的临床现状、核心挑战及未来方向,旨在为临床实践与科研探索提供参考,推动胃癌免疫治疗向精准化、个体化方向迈进。

     

    Abstract: In recent years, with the deepening understanding of the immune microenviron-ment and immune escape mechanism of gastric cancer, immunotherapy is becoming an important component of the treatment system. Immunotherapy, represented by programmed death receptor 1/programmed death receptor ligand 1 inhibitors, has expanded from the posterior line to the first line and perioperative periods, and its combination with chemotherapy, targeted therapy, as well as radio-therapy can improve the remission rate and survival outcomes of some patients. Meanwhile, chimeric antigen receptor T‑cell immunotherapy targeting antigens such as Claudin18.2, tumor vaccines, and various immune regulation strategies have also shown certain anti‑tumor activity in early clinical studies. However, there are currently three core challenges, including complex mechanisms of resis-tance, which involved immune suppression in the tumor microenvironment, regulatory T cell infiltra-tion, and epigenetic changes. There is a high incidence of immune related adverse reactions in which severe cases require immunosuppressive intervention. Patients′ heterogeneity leads to significant differences in therapeutic efficacy which lacks unified and effective predictive biomarkers. Future development should focus on integrating multidimensional biomarkers to construct a precise hierar-chical system, exploring the optimal combination mode of immunotherapy and radiotherapy, and exploring new immune checkpoint targets such as lymphocyte activation gene 3, T cell immuno-globulin mucin molecule 3, T cell immunoglobulin, and ITIM domain protein, to promote the wide-spread benefits and personalized precision treatment goals of gastric cancer immunotherapy. The author systematically reviews the clinical status, core challenges, and future directions of immuno-therapy for gastric cancer, aiming to provide reference for clinical practice and scientific research exploration, and promote the precision and individualization of gastric cancer immunotherapy.

     

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