ABSTRACT
Colorectal cancer (CRC) is the most common type of newly diagnosed cancer. Metastatic spread and multifactorial chemoresistance have limited the benefits of current therapies. Hence, it is imperative to identify new therapeutic agents to increase treatment efficacy. One of CRC's most promising immunotherapeutic targets is programmed death-1 (PD-1), a cell surface receptor that regulates immune responses. In this paper, we provide an overview of the therapeutic impact of PD-1 in the treatment of CRC. Cancer cells can exploit the PD-1 pathway by upregulating its programmed death-ligand 1 (PD-L1) ligand to evade immune surveillance. The binding of PD-L1 to PD-1 inhibits T cell function, leading to tumor immune escape. PD-1 inhibitors, such as pembrolizumab and nivolumab, block the PD-1/PD-L1 interaction. Clinical trials evaluating PD-1 inhibitors in advanced CRC have shown promising results. In patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors characterized by high mutation rates and increased immunogenicity, PD-1 blockade has demonstrated remarkable efficacy. As a result, pembrolizumab and nivolumab have received accelerated approval by regulatory authorities for the treatment of MSI-H/dMMR metastatic CRC. Additionally, combination approaches, such as combining PD-1 inhibitors with other immunotherapies or targeted agents, are being explored. Despite the success of PD-1 inhibitors in CRC, challenges still exist. Immune-related adverse events can occur and require close monitoring. In conclusion, PD-1 inhibitors have demonstrated significant therapeutic impact, particularly in patients with MSI-H/dMMR tumors.
