切换至 "中华医学电子期刊资源库"

中华普通外科学文献(电子版) ›› 2026, Vol. 20 ›› Issue (03) : 200 -206. doi: 10.3877/cma.j.issn.1674-0793.2026.03.010

综述

免疫检查点抑制剂在胃癌治疗中的应用现状
陈劲松(), 雷雪涛, 董毅   
  1. 510120 广州,广州医科大学附属第一医院胃肠外科
  • 收稿日期:2025-09-23 出版日期:2026-06-01
  • 通信作者: 陈劲松
  • 基金资助:
    国家自然科学基金项目(82072620); 广东省基础与应用基础研究基金项目(2026A1515012582)

Current status of immune checkpoint inhibitors in gastric cancer treatment

Jingsong Chen(), Xuetao Lei, Yi Dong   

  1. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
  • Received:2025-09-23 Published:2026-06-01
  • Corresponding author: Jingsong Chen
引用本文:

陈劲松, 雷雪涛, 董毅. 免疫检查点抑制剂在胃癌治疗中的应用现状[J/OL]. 中华普通外科学文献(电子版), 2026, 20(03): 200-206.

Jingsong Chen, Xuetao Lei, Yi Dong. Current status of immune checkpoint inhibitors in gastric cancer treatment[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2026, 20(03): 200-206.

胃癌是人类最常见的恶性肿瘤之一,也是癌症相关死亡的常见原因。近年来,免疫检查点抑制剂(ICIs)的出现改变了胃癌的治疗格局。程序性死亡受体1/配体1(PD-1/PD-L1)抑制剂不仅在晚期胃癌一线治疗中显示出显著的生存获益,也为局部进展期胃癌的围手术期治疗提供了新策略。本文旨在探究ICIs在胃癌一线治疗及围手术期治疗中的应用,并探讨其耐药机制、免疫相关不良反应管理、肿瘤微环境异质性等关键问题,为新型免疫治疗策略开发、联合治疗方案优化及精准个体化治疗模式提供新思路。

Gastric cancer represents one of the most common malignant tumors worldwide and leading cause of cancer-related mortality. The emergence of immune checkpoint inhibitors (ICIs) has markedly influenced the therapeutic landscape of gastric cancer in recent years. Programmed cell death protein-1 and ligand 1 (PD-1/PD-L1) inhibitors not only demonstrate significant survival benefits in the first-line treatment of advanced gastric cancer, but also provide new strategies for perioperative management of locally advanced gastric cancer. This artical aims to outline the application of ICIs in first-line and perioperative treatment of gastric cancer, and to discuss key issues including mechanisms of resistance, management of immune-related adverse events, and heterogeneity of the tumor microenvironment. These insights may shed light on novel immunotherapeutic strategies, optimization of combination regimens, and advancement of precision and individualized treatment approaches.

[1]
Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229–263.
[2]
中华医学会肿瘤学分会早诊早治学组. 胃癌早诊早治中国专家共识(2023版)[J]. 中华消化外科杂志, 2024, 23(1): 23–36.
[3]
Guan WL, He Y, Xu RH. Gastric cancer treatment: recent progress and future perspectives[J]. J Hematol Oncol, 2023, 16(1): 57.
[4]
Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial[J]. Lancet, 2021, 398(10294): 27–40.
[5]
Rha SY, Oh DY, Yañez P, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): A multicentre, randomised, double-blind, phase 3 trial[J]. Lancet Oncol, 2023, 24(11): 1181–1195.
[6]
Xu J, Jiang H, Pan Y, et al. Sintilimab plus chemotherapy for unresectable gastric or gastroesophageal junction cancer: the ORIENT-16 randomized clinical trial[J]. JAMA, 2023, 330(21): 2064–2074.
[7]
Qiu MZ, Oh DY, Kato K, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial[J]. BMJ, 2024, 385: e078876.
[8]
Shen L, Zhang Y, Li Z, et al. First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: A randomized, double-blind, phase 3 trial[J]. Nat Med, 2025, 31(4): 1163–1170.
[9]
Shitara K, Rha SY, Wyrwicz LS, et al. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): An interim analysis of the multicentre, double-blind, randomised phase 3 study[J]. Lancet Oncol, 2024, 25(2): 212–224.
[10]
Li C, Tian Y, Zheng Y, et al. Pathologic response of phase Ⅲ study: perioperative camrelizumab plus rivoceranib and chemotherapy versus chemotherapy for locally advanced gastric cancer (DRAGON Ⅳ/CAP 05)[J]. J Clin Oncol, 2025, 43(4): 464–474.
[11]
Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Perioperative durvalumab in gastric and gastroesophageal junction cancer[J]. N Engl J Med, 2025, 393(3): 217–230.
[12]
Zhao L, Liu H, Yu J, et al. Efficacy and safety of neoadjuvant toripalimab plus chemotherapy in localized deficient mismatch repair/microsatellite instability-high gastric or esophagogastric junction adenocarcinoma (NICE): A multicentre, single-arm, exploratory phase 2 study[J]. EClinicalMedicine, 2025, 87: 103421.
[13]
Sun X, Lyu J, Yang M, et al. Two-year outcomes and biomarker analysis of locally advanced gastric and gastroesophageal junction adenocarcinoma after neoadjuvant chemotherapy and immunotherapy from the phase Ⅱ WuhanUHGI001 trial[J]. Ann Surg Oncol, 2024, 31(12): 8157–8169.
[14]
Nie RC, Yuan SQ, Ding Y, et al. Perioperative tislelizumab plus chemotherapy for locally advanced gastroesophageal junction adenocarcinoma (NEOSUMMIT-03): A prospective, nonrandomized, open-label, phase 2 trial[J]. Signal Transduct Target Ther, 2025, 10(1): 60.
[15]
Choo J, Sargsyan A, Khachatryan V, et al. Advances in the management of metastatic gastric cancer: current strategies and emerging therapeutics[J]. Nat Rev Clin Oncol, 2026, 23(6): 441-458.
[16]
中国抗癌协会胃癌专业委员会, 梁寒, 朱正纲, 等. 基于PD-L1蛋白表达水平的胃癌免疫治疗专家共识(2023年版)[J]. 中国肿瘤临床, 2024, 51(2): 55–63.
[17]
Yeong J, Lum HYJ, Teo CB, et al. Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy[J]. Gastric Cancer, 2022, 25(4): 741–750.
[18]
乔旭东, 杜苗苗, 骆瑞闯. 胃充盈超声造影联合血清TGFBI、PD-L1对老年胃癌术前分期的诊断价值[J/OL]. 中华消化病与影像杂志(电子版), 2025, 15(5): 449-453.
[19]
Chen Z, Ma Y, Chen J. Applications and challenges of immunotherapy in the management of gastric adenocarcinoma: current status and future perspectives[J]. World J Surg Oncol, 2025, 23(1): 92.
[20]
Shitara K, Van Cutsem E, Bang YJ, et al. Efficacy and safety of pembrolizumab or pembrolizumab plus chemotherapy vs chemotherapy alone for patients with first-line, advanced gastric cancer: the KEYNOTE-062 phase 3 randomized clinical trial[J]. JAMA Oncol, 2020, 6(10): 1571–1580.
[21]
André T, Tougeron D, Piessen G, et al. Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in localized deficient mismatch repair/microsatellite instability-high gastric or esophagogastric junction adenocarcinoma: the GERCOR NEONIPIGA phase Ⅱ study[J]. J Clin Oncol, 2023, 41(2): 255–265.
[22]
Janjigian YY, Kawazoe A, Yañez P, et al. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer[J]. Nature, 2021, 600(7890): 727–730.
[23]
Kelly RJ, Landon BV, Zaidi AH, et al. Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: A phase Ⅰb trial and ctDNA analyses[J]. Nat Med, 2024, 30(4): 1023–1034.
[24]
Luo D, Zhou J, Ruan S, et al. Overcoming immunotherapy resistance in gastric cancer: insights into mechanisms and emerging strategies[J]. Cell Death Dis, 2025, 16(1): 75.
[25]
Yasuda T, Wang YA. Gastric cancer immunosuppressive microenvironment heterogeneity: implications for therapy development[J]. Trends Cancer, 2024, 10(7): 627–642.
[26]
许建江, 刘涛, 姜雷. PD-1抑制剂治疗胃癌耐药机制的研究进展[J]. 中国肿瘤临床, 2025, 52(4): 188–192.
[27]
Han Z, Cheng S, Dai D, et al. The gut microbiome affects response of treatments in HER2-negative advanced gastric cancer[J]. Clin Transl Med, 2023, 13(7): e1312.
[28]
Ling Z, Shao L, Liu X, et al. Regulatory T cells and plasmacytoid dendritic cells within the tumor microenvironment in gastric cancer are correlated with gastric microbiota dysbiosis: A preliminary study[J]. Front Immunol, 2019, 10: 533.
[29]
Yin Q, Wu L, Han L, et al. Immune-related adverse events of immune checkpoint inhibitors: A review[J]. Front Immunol, 2023, 14: 1167975.
[30]
Karaviti D, Kani ER, Karaviti E, et al. Thyroid disorders induced by immune checkpoint inhibitors[J]. Endocrine, 2024, 85(1): 67–79.
[31]
Di Dalmazi G, Ippolito S, Lupi I, et al. Hypophysitis induced by immune checkpoint inhibitors: A 10-year assessment[J]. Expert Rev Endocrinol Metab, 2019, 14(6): 381–398.
[32]
Lin MX, Zang D, Liu CG, et al. Immune checkpoint inhibitor-related pneumonitis: research advances in prediction and management[J]. Front Immunol, 2024, 15: 1266850.
[33]
Bagchi S, Yuan R, Engleman EG. Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance[J]. Annu Rev Pathol, 2021, 16: 223–249.
[34]
Zeng D, Yu Y, Qiu W, et al. Immunotyping the tumor microenvironment reveals molecular heterogeneity for personalized immunotherapy in cancer[J]. Adv Sci (Weinh), 2025, 12(25): e2417593.
[35]
Janjigian YY, Oh DY, Pelster M, et al. Domvanalimab and zimberelimab in advanced gastric, gastroesophageal junction or esophageal cancer: A phase 2 trial[J]. Nat Med, 2025, 31(12): 4274–4280.
[36]
Shitara K, Bang Y J, Iwasa S, et al. Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial[J]. Nat Med, 2024, 30(7): 1933–1942.
[37]
Peng Z, Chen P, Lu J, et al. Trastuzumab deruxtecan in patients from China with previously treated human epidermal growth factor receptor 2-positive locally advanced/metastatic gastric or gastroesophageal junction adenocarcinoma (DESTINY-Gastric06): results from a single-arm, multicenter, phase 2 trial[J]. EClinicalMedicine, 2025, 87: 103404.
[38]
Van Cutsem E, di Bartolomeo M, Smyth E, et al. Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): primary and updated analyses from a single-arm, phase 2 study[J]. Lancet Oncol, 2023, 24(7): 744–756.
[1] 张俊峰, 牛越, 陈鹏. 局部进展期肾细胞癌新辅助和辅助治疗策略的现实挑战与未来发展[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2026, 20(03): 248-254.
[2] 陈宇煊, 方建雄, 曹嘉正. 基于DNA甲基化、基因突变及转录组的尿液基因组学检测在尿路上皮癌诊断中的应用[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2026, 20(03): 341-345.
[3] 陈希, 范海华, 倪婷婷, 宋丽, 邵丽丽. cfDNA、NLR及PD-L1联合检测对42例非小细胞肺癌患者免疫治疗疗效的预测意义[J/OL]. 中华肺部疾病杂志(电子版), 2026, 19(03): 405-410.
[4] 陈惠姗, 曾惠清. 生物标志物在诊断渗出性和漏出性胸腔积液鉴别诊断中的研究进展[J/OL]. 中华肺部疾病杂志(电子版), 2026, 19(02): 330-334.
[5] 陆军, 宋勇. 治疗性肿瘤疫苗应用于肺癌的临床研究与前沿进展[J/OL]. 中华肺部疾病杂志(电子版), 2026, 19(02): 335-340.
[6] 陈力, 高心怡, 刘心怡, 邵幼林. 血清降钙素原在社区获得性肺炎严重程度评估及抗生素使用指导中的临床应用研究进展[J/OL]. 中华肺部疾病杂志(电子版), 2026, 19(02): 341-345.
[7] 刘佳铭, 文健, 孙晓容, 钟瑶, 张雯. 慢性阻塞性肺疾病合并肺癌免疫检查点抑制剂相关重症皮疹一例[J/OL]. 中华肺部疾病杂志(电子版), 2026, 19(02): 353-355.
[8] 曾桂能, 杨鹏辉, 刘荣. 表达IL-21的重组溶瘤流感病毒在胰腺癌中的抗肿瘤及免疫激活作用研究[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(03): 129-139.
[9] 刘国臣, 安嘉伟, 朱俊宇, 代伟宏, 李芬. LCN2在脓毒症中的作用机制研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(03): 162-169.
[10] 王泽宁, 费振浩, 陈业盛, 孙志为. 基于肝癌体积-时间窗的个体化TACE-MWA序贯治疗策略及其机制探讨[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(03): 307-316.
[11] 周正, 胡帅, 谢茂云, 郑希彦, 刘婷, 林志群, 陈贤清, 杜飞, 史宪杰. 可切除肝癌围手术期辅助治疗研究进展[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(03): 317-325.
[12] 贾生雄, 徐岩, 贺小军, 谭凯, 杜锡林. CD47-SIRPα轴调控及CD47靶向治疗:破解胰腺癌免疫治疗耐药新策略[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(03): 337-345.
[13] 黄思捷, 张惠勇, 郭小辉, 徐成润. 全身炎症反应指数对晚期肝癌患者TACE联合靶向免疫治疗预后的预测价值[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(03): 355-361.
[14] 叶永青, 罗帅妹, 温顺前, 陈俊鹏, 张先华, 黄丽云, 劳琪君, 巫青. 中晚期肝细胞癌靶向免疫治疗进展[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(03): 413-419.
[15] 叶林森, 杨扬. 进展期肝癌治疗困境与探索:综述与展望[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(03): 290-298.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?