Boutin Mélina, Gill Sharlene
BC Cancer, University of British Columbia, Vancouver, BC, Canada.
Centre Intégré de Cancérologie de la Montérégie-Centre, Université de Sherbrooke, Greenfield Park, QC, Canada.
Ther Adv Med Oncol. 2023 Mar 29;15:17588359231162577. doi: 10.1177/17588359231162577. eCollection 2023.
High microsatellite instability (MSI-H)/deficient mismatch repair (dMMR) phenotype is a distinct molecular signature across gastrointestinal cancers characterized by high tumor mutational burden and high neoantigen load. Tumors harboring dMMR are highly immunogenic and heavily infiltrated by immune cells; consequently, they are uniquely vulnerable to therapeutic strategies enhancing immune antitumor response such as checkpoint inhibitors. The MSI-H/dMMR phenotype arose as a powerful predictor of response to immune checkpoint inhibitors with evidence supporting significantly improved outcomes in the metastatic setting. On the other hand, the genomic instability characteristic of MSI-H/dMMR tumors appears to be associated with decreased sensitivity to chemotherapy, and the benefits of standard adjuvant or neoadjuvant chemotherapy approaches in this subtype are being increasingly questioned. Here, we review the prognostic and predictive impact of MMR status in localized gastric and colorectal cancers, and highlight the emerging clinical data incorporating checkpoint inhibitors in the neoadjuvant setting.
高微卫星不稳定性（MSI-H）/错配修复缺陷（dMMR）表型是胃肠道癌症中一种独特的分子特征，其特点是肿瘤突变负担高和新抗原负荷高。携带dMMR的肿瘤具有高度免疫原性，且有大量免疫细胞浸润；因此，它们对增强免疫抗肿瘤反应的治疗策略（如检查点抑制剂）特别敏感。MSI-H/dMMR表型已成为免疫检查点抑制剂反应的有力预测指标，有证据表明在转移性情况下其疗效显著改善。另一方面，MSI-H/dMMR肿瘤的基因组不稳定特征似乎与化疗敏感性降低有关，该亚型中标准辅助或新辅助化疗方法的益处正受到越来越多的质疑。在此，我们综述错配修复状态在局限性胃癌和结直肠癌中的预后和预测影响，并强调在新辅助治疗中纳入检查点抑制剂的新出现的临床数据。
