Abstract 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.
