Colorectal cancer (CRC) is the third most prevalent cancer in the world. The PD-1/PD-L1 pathway plays a crucial role in modulating immune response to cancer, and PD-L1 expression has been observed in tumor and immune cells within the tumor microenvironment of CRC. Thus, immunotherapy drugs, specifically checkpoint inhibitors, have been developed to target the PD-1/PD-L1 signaling pathway, thereby inhibiting the interaction between PD-1 and PD-L1 and restoring T-cell function in cancer cells. However, the emergence of resistance mechanisms can reduce the efficacy of these treatments. To counter this, monoclonal antibodies (mAbs) have been used to improve the efficacy of CRC treatments. mAbs such as nivolumab and pembrolizumab are currently approved for CRC treatment. These antibodies impede immune checkpoint receptors, including PD-1/PD-L1, and their combination therapy shows promise in the treatment of advanced CRC. This review presents a concise overview of the use of the PD-1/PD-L1 blockade as a therapeutic strategy for CRC using monoclonal antibodies and combination therapies. Additionally, this article outlines the function of PD-1/PD-L1 as an immune response suppressor in the CRC microenvironment as well as the potential advantages of administering inflammatory agents for CRC treatment. Finally, this review analyzes the outcomes of clinical trials to examine the challenges of anti-PD-1/PD-L1 therapeutic resistance.
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