免疫检查点抑制剂（ICIs）彻底改变了治疗缺失配对修复/微卫星不稳定性高（MMMR-D/MSI-H）结直肠癌（CRC）的范例。MMR-D/MSI-H CRC具有独特的分子特征，包括错位的突变（frameshift alterations），导致突变相关新抗原（MANA）生成，为MANA驱动的T细胞初步进行和抗肿瘤免疫提供了理想的分子框架。这些生物学特征催生出在MMR-D/MSI-H CRC患者中ICIs的快速药物开发。在晚期疾病中使用ICIs观察到深刻和持久的反应，刺激了对早期MMR-D/MSI-H CRC患者进行ICIs临床试验的开发。最近，中和抑制剂嗜铬细胞瘤抗原D（dostarlimab）单药治疗非手术处理MMR-D/MSI-H直肠癌以及nivolumab和ipilimumab的NICHE试验用于MMR-D/MSI-H结肠癌的新辅助治疗取得了开创性的成果。虽然ICIs在MMR-D/MSI-H直肠癌患者中的非手术治疗将有可能定义我们当前的治疗方法，但对于结肠癌，新辅助ICIs治疗的治疗目标可能有所不同，因为结肠癌的非手术治疗尚未得到很好的确认。在这里，我们概述了ICIs治疗MMR-D/MSI-H结肠癌和直肠癌早期患者的最新进展，并详细阐述了这个独特CRC亚组的未来治疗范例。

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigm of mismatch repair-deficient/microsatellite instability-high (MMMR-D/MSI-H) colorectal cancer (CRC). Unique molecular features of MMR-D/MSI-H CRC with frameshift alterations, which result in mutation-associated neoantigen (MANA) generation, create an ideal molecular framework for MANA-driven T-cell priming and antitumor immunity. These biologic characteristics of MMR-D/MSI-H CRC resulted in rapid drug development with ICIs for patients with MMR-D/MSI-H CRC. Observed deep and durable responses with the use of ICIs in advanced-stage disease have stimulated the development of clinical trials with ICIs for patients with early-stage MMR-D/MSI-H CRC. Most recently, neoadjuvant dostarlimab monotherapy for nonoperative management of MMR-D/MSI-H rectal cancer and neoadjuvant NICHE trial with nivolumab and ipilimumab for MMR-D/MSI-H colon cancer resulted in groundbreaking results. Although nonoperative management of patients with MMR-D/MSI-H rectal cancer with ICIs will potentially define our current therapeutic approach, therapeutic goals of neoadjuvant ICI therapy for patients with MMR-D/MSI-H colon cancer may differ given that nonoperative management has not been well established for colon cancer. Herein, we overview recent advancements in ICI-based therapies for patients with early-stage MMR-D/MSI-H colon and rectal cancer and elaborate on the future treatment paradigm of this unique subgroup of CRC.