As the third malignant tumor in the world, colorectal cancer has caused a great burden on the society. In recent years, immunotherapy has been dominated by immune checkpoint inhibitors (ICIs). ICIs are highly effective in patients with microsatellite instability-high (MSI-H) or deficiency of mismatch repair (dMMR) metastatic colorectal cancer (mCRC), which provide new ways to treat advanced colorectal cancer. Although ICIs achieve significant therapeutic effects in mCRC patients with dMMR/MSI-H subtypes, only a few members of CRC patients can benefit from ICIs due to primary immune resistance. Besides, patients who benefit from initial ICIs may develop the secondary therapeutic resistance during the treatment process, which may ultimately lead to disease progression. However, tumor tissue is interdependent with the tumor microenvironment (TME), and various molecules and cells in the microenvironment have complex effects on the development of the tumor and immunotherapy. Among them, the composition change of TME may have a close relationship to immune resistance. Therefore, the mechanisms between immune resistance and the tumor microenvironment were elaborated to summarize and explore the possible mechanisms of immune resistance in colorectal cancer.
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