Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
Zhejiang University School of Medicine, Hangzhou, China.
Ann Surg Oncol. 2023 Dec;30(13):8572-8587. doi: 10.1245/s10434-023-14103-0. Epub 2023 Sep 4.
Gastric cancer (GC) remains one of the world's most common and fatal malignant tumors. With a refined understanding of molecular typing in recent years, microsatellite instability (MSI) has become a major molecular typing approach for gastric cancer. MSI is well recognized for its important role during the immunotherapy of advanced GC. However, its value remains unclear in resectable gastric cancer. The reported incidence of microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) in resectable gastric cancer varies widely, with no consensus reached on the value of postoperative adjuvant therapy in patients with MSI-H/dMMR resectable GC. It has been established that MSI-H/dMMR tumor cells can elicit an endogenous immune antitumor response and ubiquitously express immune checkpoint ligands such as PD-1 or PD-L1. On the basis of these considerations, MSI-H/dMMR resectable GCs are responsive to adjuvant immunotherapy, although limited research has hitherto been conducted. In this review, we comprehensively describe the differences in geographic distribution and pathological stages in patients with MSI-H/dMMR with resectable gastric cancer and explore the value of adjuvant chemotherapy and immunotherapy on MSI-H/dMMR to provide a foothold for the individualized treatment of this patient population.
胃癌(GC)仍然是世界上最常见和最致命的恶性肿瘤之一。近年来,随着对分子分型的深入了解,微卫星不稳定性(MSI)已成为胃癌的主要分子分型方法。MSI 在晚期 GC 的免疫治疗中具有重要作用,这一点已得到广泛认可。然而,其在可切除性 GC 中的价值仍不清楚。报道的可切除性胃癌中微卫星不稳定高(MSI-H)/错配修复缺陷(dMMR)的发生率差异很大,对于 MSI-H/dMMR 可切除 GC 患者术后辅助治疗的价值尚无共识。已经证实,MSI-H/dMMR 肿瘤细胞可以引发内源性免疫抗肿瘤反应,并普遍表达免疫检查点配体,如 PD-1 或 PD-L1。基于这些考虑,MSI-H/dMMR 可切除 GC 对辅助免疫治疗有反应,尽管迄今为止研究有限。在这篇综述中,我们全面描述了 MSI-H/dMMR 可切除性胃癌患者在地理分布和病理分期上的差异,并探讨了辅助化疗和免疫治疗对 MSI-H/dMMR 的价值,为这一患者群体的个体化治疗提供了依据。