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免疫检查点抑制剂联合治疗在局部晚期胃癌或胃食管交界腺癌围手术期治疗中的临床意义

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

作者信息

Zhu Z G

机构信息

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.

出版信息

Zhonghua Wei Chang Wai Ke Za Zhi. 2024 Jul 25;27(7):659-665. doi: 10.3760/cma.j.cn441530-20240507-00166.

Abstract

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.

摘要

免疫检查点抑制剂(ICI)的临床应用为局部晚期胃癌(LAGC)和胃食管交界腺癌(AGEJ)提供了新的治疗方式,其关键益处是能提高治愈率。这些药物已成为部分特定病例围手术期标准治疗的一部分,例如根据肿瘤免疫组化、基因检测或分子特征判断为微卫星高度不稳定/错配修复缺陷(MSI-H/dMMR)、联合阳性评分(CPS)高表达(≥5)或 Epstein-Barr 病毒(EBV)阳性、MSI-H 以及微卫星稳定/TP53 阳性的肿瘤。深入了解“冷”肿瘤和“热”肿瘤中的免疫反应机制,有助于我们更好地识别 ICI 的受益患者,并进一步为将无反应的“冷”肿瘤转化为有反应的“热”肿瘤提供理论依据,从而使无反应者也能从 ICI 免疫治疗中获益。最近的几项临床试验清楚地证明了 ICI 与化疗或放化疗联合,以及 ICI 与抗人表皮生长因子受体 2(HER2)或抗血管内皮生长因子/血管内皮生长因子受体(VEGF/VEGFR)和化疗联合具有协同和互补作用。与单纯化疗相比,联合治疗可显著提高病理完全缓解(pCR)、主要缓解率(MRR)或 ypT0N0,并有望改善预后。本文回顾了近年来一系列关于 ICI 在 LAGC/AGEJ 围手术期与其他治疗方式联合应用的临床试验结果,旨在拓展对 LAGC/AGEJ 当前标准新辅助和辅助治疗的讨论,并探索未来新的围手术期联合免疫治疗的可行性。

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