| Summary: | Immune checkpoint inhibitors (ICIs) have significantly advanced colorectal cancer treatment in recent years. Antibodies that target the proteins programmed cell death-1 (PD-1), programmed cell death-1 ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are among the ICIs that are currently being used in clinical practice. However, in colorectal cancer, ICI's effectiveness is limited to a fraction of patients with microsatellite instability-high (MSI-H), which only accounts for about 5% of advanced cases. The tumor microenvironment and intrinsic changes in tumor cells are just a couple of the many mechanisms that play a role in ICI primary or secondary resistance. In order to advance precision medicine and broaden the population benefiting from ICI, this paper highlights the main underlying mechanisms of ICIs resistance and suggested techniques to overcome it.
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