作者：杨欢，彭建军

单位：中山大学附属第一医院 胃肠外科中心， 广东 广州 510080

Authors: Yang Huan，Peng Jianjun

Unit: Center for Gastrointestinal Surgery，First Affiliated Hospital of Sun Yat-Sen University，Guangzhou 510080，Guangdong，China

摘要：

胃癌是我国主要瘤种之一，大部分胃癌在诊断时已经进展至中晚期。以氟尿嘧啶类、铂类、紫杉醇类药物为核心的化疗是中晚期胃癌的主要治疗手段。然而，化疗存在原发性耐药、继发性耐药和较高的毒性问题。人表皮生长因子受体2(HER-2)是重要的肿瘤治疗靶点，HER-2阳性胃癌对HER-2靶向治疗药曲妥珠单抗有效，但较低的阳性表达率限制了HER-2靶向药物在胃癌中的应用。抗血管生成治疗在胃癌中也表现出一定效果，包括小分子多靶点酪氨酸激酶抑制剂阿帕替尼、血管内皮生长因子受体（VEGFR）封闭抗体雷莫西尤单抗被推荐用于二线以上晚期胃癌的治疗。目前胃癌化疗、靶向治疗选择仍然有限，治疗效果不够理想。近年来免疫治疗蓬勃发展，免疫检查点抑制剂已经开始广泛应用于胃癌。以程序性死亡蛋白1(PD-1)抗体为核心的免疫检查点抑制剂对胃癌显示出良好的效果，逐步从二线提高到一线，在胃癌的治疗中发挥越来越大的作用。其他免疫疗法，包括嵌合抗原受体T细胞（CAR-T）等也在快速临床开发之中。免疫疗法的出现让胃癌的治疗面貌大为改观，更多的免疫疗法也有望在不久的将来不断涌现。本文对胃癌免疫治疗的最新临床进展展开综述，包括免疫检查点抑制剂、过继性免疫细胞疗法、肿瘤疫苗等。 

关键词：胃癌； 免疫治疗； 检查点抑制剂； 过继性免疫细胞； 溶瘤病毒； 肿瘤疫苗； 免疫调节剂

Abstract：

Gastric cancer is one of the major tumor in China，and most gastric cancers have progressed to the middle or advanced stages at diagnosis. The main treatment for advanced gastric cancer is chemotherapy with fluorouracil，platinum and paclitaxel. However，chemotherapy has disadvantages with primary resistance，secondary resistance and higher toxicity. Human epidermal growth factor receptor-2 （HER-2） is an important tumor therapeutic target. The HER2-targeted therapy trastuzumab is effective against HER2-positive gastric cancer，but the low positive rate limits the use of HER2 -targeted drugs in gastric cancer. Anti -angiogenic therapy has also shown some effect in gastric cancer ，including small molecule multi -target tyrosine kinase inhibitor apatinib and the vascular endothelial growth factor receptor （VEGFR）-bloking antibody ramucirumab being recommended for the treatment of advanced gastric cancer above the second line. In general，the current chemotherapy and targeted therapy options for gastric cancer are still limited，and the treatment effect is not ideal. Immunotherapy has flourished in recent years ，and immune checkpoint inhibitors have begun to be widely used in gastric cancer. Immune checkpoint inhibitors with programmed cell death-1 （PD-1） antibody as the core have shown good effects on gastric cancer ， gradually improving from second line to first line，and playing an increasingly important role in the treatment of gastric cancer. Other immunotherapies，including CAR-T，are also under rapid development. The advent of immunotherapy has greatly changed the treatment of gastric cancer ，and more immunotherapies are expected to emerge in the near future. In this article，we review the latest clinical progress of gastric cancer immunotherapy，including immune checkpoint inhibitors，adoptive immune cell transfer therapy，tumor vaccines，etc.

Key Words:  Gastric cancer; Immunotherapy; Checkpoint inhibitors; Adoptive immune cells; Oncolytic viruses; Tumor vaccines; Immunomodulators