围手术期联合免疫检查点抑制剂治疗局部进展期胃癌或胃食管结合部腺癌的临床意义  

Clinical significance of combined therapy with immune checkpoint inhibitor in perioperative treatment for locally advanced gastric cancer or adenocarcinoma of gastroesophageal junction

作　　者：朱正纲[1] Zhu Zhenggang(Department of Surgery,Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai Institute of Digestive Surgery,Shanghai Key Laboratory of Stomach Neoplasms,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院外科,上海消化外科研究所,上海市胃肿瘤重点实验室,上海200025

出　　处：《中华胃肠外科杂志》2024年第7期659-665,共7页Chinese Journal of Gastrointestinal Surgery

基　　金：国家自然科学基金(81871904)。

摘　　要：临床应用免疫检查点抑制剂(ICI)为局部进展期胃癌(LAGC)或胃食管结合部腺癌(AGEJ)提供了新的治疗手段,获得了更高的治愈率。通过免疫组织化学、基因检测与分子特征分析,发现对于错配修复缺陷(dMMR)/微卫星高度不稳定(MSI-H)、PD-L1综合阳性评分(CPS)≥5或EB病毒高表达、MSI-H和微卫星稳定(MSS)/TP53阳性的肿瘤患者,在围手术期联合应用ICI可作为标准的治疗方案。深入了解“冷”和“热”肿瘤的免疫反应机制,能帮助更好地筛选ICI治疗获益者;同时可为将无应答的“冷”肿瘤转化为有应答的“热”肿瘤提供理论依据,使无应答患者能受益于ICI免疫治疗。最近的一些临床试验明确地表明,ICI与化疗或放化疗联合,或者ICI联合抗HER-2或抗血管内皮生长因子(VEGF)/VEGF受体(VEGFR)与化疗具有多药协同与互补作用;与单纯化疗相比,联合治疗能明显提高病理完全缓解率、主要缓解率或ypT0N0比例等,并有望改善患者预后。本文总结了近年来在LAGC/AGEJ围手术期联合应用ICI与其他治疗模式的一系列临床试验结果,深入讨论了ICI应用于LAGC/AGEJ新辅助和辅助治疗的现状,探讨了未来新的围手术期免疫联合治疗的可行性。The clinical application of immune checkpoint inhibitor(ICI)offers novel treatment modality for locally advanced gastric cancer(LAGC)and adenocarcinoma of the gastroesophageal junction(AGEJ),with the crucial benefit of providing higher cure rates.These agents have become part of standard treatments in the perioperative setting for selected cases,such as tumor with MSI-H/dMMR,high expression of CPS(≥5)or EBV(+),MSI-H and MSS/TP53+according to tumor immunohistochemical,genetic testing or molecular characterization.An in-depth understanding of the immune response mechanisms in"cold"and"hot"tumors enables us to better identify ICI beneficiary and further provide a rationale for converting nonresponsive"cold"tumors into responsive"hot"tumors,subsequently allowing nonresponders to benefit from ICI immunotherapy.Several recent clinical trials clearly demonstrated a synergistic and complementary effect of combining ICI with chemotherapy or chemoradiotherapy,as well as combining ICI with anti-HER2 or anti-VEGF/VEGFR and chemotherapy.Compared with chemotherapy alone,the combination treatment can significantly improve pCR,MRR or ypT0N0,and is expected to improve the prognosis.This article reviews the results of a series of clinical trials in recent years in the field of perioperative application of ICI with other modalities in LAGC/AGEJ,aiming at expanding upon the discussion of current standard neoadjuvant and adjuvant therapies for LAGC/AGEJ and exploring the feasibility of new perioperative combined immunotherapy in the future.

关 键 词：胃肿瘤 局部进展期 胃食管结合部腺癌 围手术期治疗 免疫检查点抑制剂 病理完全缓解 

分 类 号：R735.2[医药卫生—肿瘤]