Over the past decade, immunotherapy has been shown to have antitumor activity in a variety of solid tumors, such as melanoma, renal cell carcinoma, and non-small cell lung cancer, keeping a lead in a new era of tumor immunotherapy. Colorectal cancer with high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR) is sensitive to immune checkpoint inhibitors (ICIs). ICIs monotherapy and ICIs combination therapy have made breakthroughs in the treatment of MSI-H/dMMR CRC. At present, a variety of ICIs have been approved for first- and post-line treatment in patients with CRC. However, MSI-H/dMMR type tumors only account for 5% of metastatic CRC, and the most CRCs were microsatellite stable (MSS) or mismatch repair proficient (pMMR). Many clinical trials are exploring effective treatments for patients with MSS/pMMR CRC, and the combination of ICIs and drugs with different mechanisms is expected to improve the efficacy of MSS/pMMR CRC patients. In the future, attention should be paid to finding the potential therapeutic markers of ICIs and the drug resistance mechanism of ICIs, so as to break through the immune tolerance of MSS/pMMR CRC patients.
在过去的十年中，免疫治疗已被证实在黑色素瘤、肾细胞癌、非小细胞肺癌等多种实体肿瘤中具有抗肿瘤活性，开启了肿瘤免疫治疗的新时代。具有微卫星高度不稳定性(microsatellite instability-high，MSI-H)或错配修复缺陷(mismatch repair deficient，dMMR)的结直肠癌(colorectal cancer，CRC)对免疫检查点抑制剂(immune checkpoint inhibitors，ICIs)敏感，ICIs单药治疗及ICIs联合治疗在MSI-H/dMMR型CRC治疗中取得突破性进展，目前已有多种ICIs被批准用于CRC患者的一线及后线治疗。然而，MSI-H/dMMR型肿瘤仅占转移性CRC的5%，大部分CRC为微卫星稳定(microsatellite stable，MSS)型或者错配修复完整(mismatch repair proficient，pMMR)型。许多临床试验正在探索MSS/pMMR型CRC患者的有效治疗方法，ICIs和不同机制药物的联合治疗有望提高MSS/pMMR型CRC患者的疗效。未来应更加注重寻找ICIs的潜在疗效标志物和ICIs的耐药机制，突破MSS/pMMR型CRC患者的免疫耐受。.
Keywords: colorectal cancer; cytotoxic T lymphocyte antigen 4; immune checkpoint inhibitors; programmed death ligand-1; programmed death-1.