结直肠癌是消化系统最常见的恶性肿瘤,发病率在肿瘤中排第 3 位,死亡率排第 2 位,对患者的生存期和生活质量 造成了严重威胁。 免疫检查点抑制剂(ICIs)已成为错配修复缺陷或微卫星高度不稳定(MSI-H/ dMMR)结直肠癌的一线及后 线治疗方案的重要组成,然而,MSI-H/ dMMR 结直肠癌仅占所有转移性结直肠癌的 4% ~ 5%,且对于微卫星稳定型(MSS)结 直肠癌患者,由于肿瘤的异质性和复杂的免疫异质性肿瘤微环境,ICIs 单药往往无法克服这些因子而出现应答率不高或出现 继发性耐药,因此仅使用单一 ICIs 基本无效。 目前多采用联合治疗策略如抗程序性死亡蛋白受体-1(PD-1)和细胞毒性 T 淋 巴细胞相关蛋白 4(CTLA-4)的联合治疗,ICIs 联合放疗,ICIs 联合细胞外信号调节激酶(MEK)抑制剂和血管内皮生长因子 (VEGF)抑制剂,以及 ICIs 联合溶瘤病毒等提高 MSS / 错配修复功能完整( pMMR)结直肠癌患者对治疗的应答率。 虽然上述 联合治疗策略取得不错的近期疗效,在治疗转移性结直肠癌(mCRC)患者中很有前景,但多为单臂小样本探索性研究,数据指向 并不完全稳定一致,安全性和有效性还需更多大样本的前瞻性临床试验验证,同时也需Ⅲ期临床研究的确认和证实。 本文旨在 对 MSS 结直肠癌 ICIs 联合治疗研究进展进行综述。

Colorectal cancer is the most common malignant tumor of digestive system ranking the third in incidence and the second in mortality which poses a serious threat to the survival and quality of life of patients. Immune checkpoint inhibitors have become an important component of the first -line and late -line treatment regimens for MSI -H/ dMMR colorectal cancer. However MSI-H/ dMMR colorectal cancer accounts for only 4% ~ 5% of all metastatic colorectal cancers and for MSS / pMMR colorectal cancer patients due to tumor heterogeneity and complex immunologically heterogeneous tumor microenvironment immune checkpoint inhibitors alone often cannot overcome these factors and have low response rate or secondary drug resistance so the use of single ICIs is basically ineffective. At present combination therapy strategies such as anti-PD-1 and CTLA-4 ICIs combined with radiotherapy ICIs combined with MEK inhibitor and VEGF inhibitor ICIs combined with oncolytic virus double immunotherapy combined with targeted therapy are adopted to improve the response rate of MSS / pMMR colorectal cancer patients. Although the above -mentioned combination therapy strategy has achieved good short-term efficacy and has great prospects in the treatment of mCRC patients most of them are single - arm small - sample exploratory studies and the data are not completely stable and consistent. The safety and effectiveness need to be verified by more large-sample prospective clinical trials and also need to be confirmed and confirmed by phase Ⅲ clinical studies. This article aims to review the progress of ICIs combination therapy for MSS colorectal cancer.