免疫检查点抑制剂在结直肠癌中的应用：当前和未来的策略

免疫检查点抑制剂（ICIs）主要包括帕博利珠单抗、纳武单抗和伊匹木单抗，已经改变了多种类型肿瘤的标准治疗方案。对于结直肠癌（CRC），肿瘤中微卫星不稳定（MSI）或错配修复（MMR）的状态是影响ICIs疗效的最关键因素。高水平MSI（MSI-H）或MMR缺陷（dMMR）的转移性CRC（mCRC）通常有浸润T细胞的肿瘤微环境，与对ICIs的良好反应相关，但MSI-H/dMMR的比例不足5%。帕博利珠单抗和纳武单抗联合或不联合伊匹木单抗已被纳入MSI-H/dMMR mCRC的标准治疗方案。与此相反，微卫星稳定（MSS）或错配修复稳定（pMMR）的mCRC的肿瘤微环境中T细胞浸润程度低被认为是ICIs的主要耐药机制。笔者回顾现有ICIs治疗CRC的临床数据和正在进行的部分临床试验，讨论可能存在的不足。

Application of immune checkpoint inhibitors in colorectal cancer: current and future strategies

Immune checkpoint inhibitors (ICIs) mainly include pembrolizumab, nivolumab and ipilimumab, which have changed the standard treatment for many types of cancer. In colorectal cancer (CRC), the status of microsatellite instability (MSI) or mismatch repair (MMR) is the most important factor affecting the efficacy of ICIs. Metastatic CRC (mCRC) with microsatellite instability-high (MSI-H) or MMR deficiency (dMMR) usually has a tumor microenvironment T-cell infiltration and is associated with a good response to ICIs, but the proportion of mSI-H/dMMR accounts for less than 5% of the mCRC. Paprizumab and navumab with or without combination of ipilimumab have been included in the standard treatment regimen for MSI-H/dMMR mCRC. In contrast, low T-cell infiltration in tumor microenvironments of mCRCs with microsatellite stable (MSS) or mismatch repair stable (pMMR) is considered to be the main mechanism of ICIs resistance. Here, the authors review the existing clinical data and some ongoing clinical trials of ICIs for CRC treatment, and discuss the possible limitations.