缺乏错配修复（dMMR）途径/微卫星不稳定性（MSI）的结直肠癌（CRC）的特点是肿瘤微环境中的高突变负荷和免疫细胞浸润。与这些发现一致的是，临床试验已证明免疫检查点抑制剂 (ICIs) 在 dMMR/MSI 转移性 CRC (mCRC) 患者中以及最近在接受新辅助治疗的早期疾病 CRC 患者中具有显着活性。然而，尽管缓解率很高并具有持久的临床益处，但仍有一小部分转移性结直肠癌患者（高达 30%）在接受单药抗程序性细胞死亡 1 (PD-1) 抗体治疗时表现出疾病进展。本文讨论了与 dMMR/MSI mCRC 患者在 ICI 治疗期间早期进展相关的三个主要原因，即误诊、假性进展和肿瘤异质性。虽然假性进展可能不会发挥相关作用，但临床研究数据表明，一些在 ICI 上快速进展的 dMMR/MSI CRC 病例可能会被误诊，这强调了正确诊断的重要性。更重要的是，有证据表明 dMMR/MSI mCRC 是一组对 ICI 具有不同敏感性的异质性肿瘤。因此，我们提出新的诊断和治疗策略来改善 dMMR/MSI CRC 患者的预后。© 作者 2024。

Colorectal carcinoma (CRC) with deficiency of the deficient mismatch repair (dMMR) pathway/microsatellite instability (MSI) is characterized by a high mutation load and infiltration of immune cells in the tumor microenvironment. In agreement with these findings, clinical trials have demonstrated a significant activity of immune checkpoint inhibitors (ICIs) in dMMR/MSI metastatic CRC (mCRC) patients and, more recently, in CRC patients with early disease undergoing neoadjuvant therapy. However, despite high response rates and durable clinical benefits, a fraction of mCRC patients, up to 30%, showed progressive disease when treated with single agent anti-programmed cell death 1 (PD-1) antibody. This article discusses the three main causes that have been associated with early progression of dMMR/MSI mCRC patients while on treatment with ICIs, i.e., misdiagnosis, pseudoprogression and tumor heterogeneity. While pseudoprogression probably does not play a relevant role, data from clinical studies demonstrate that some dMMR/MSI CRC cases with rapid progression on ICIs may be misdiagnosed, underlining the importance of correct diagnostics. More importantly, evidence suggests that dMMR/MSI mCRC is a heterogeneous group of tumors with different sensitivity to ICIs. Therefore, we propose novel diagnostic and therapeutic strategies to improve the outcome of dMMR/MSI CRC patients.© The Author(s) 2024.