Role of Programmed Death Ligand 1 in Colorectal Cancer

Colorectal cancer (CRC) is a significant cause of cancer- related deaths worldwide, and its incidence and mortality are increasing each year. It accounts for approximately 10% of all annually diagnosed cancers and cancer-related deaths worldwide\[1\] Most colon cancer is sporadic, and approximately 5 percent are due to an inherited genetic mutation, mostly due to Lynch syndrome (hereditary nonpolyposis colon cancer or HNPCC) and familial adenomatous polyposis (FAP). The transition from normal colon epithelium to invasive cancer takes several years and most commonly follows a sequence characterized by the accumulation of genetic mutations, adenoma formation, and subsequent carcinogenesis (adenoma-carcinoma sequence). Programmed death-1 (PD-1) is an immunoglobulin superfamily type I transmembrane glycoprotein consisting of 288 amino acids, which is expressed on different immune cells, especially on T cells\[2\]. Programmed death ligand 1 (PD-L1) is one ligand of PD-1. Soluble programmed death ligand 1 (sPD-L1) is released from PD-L1-positive cells, which binds to receptor of PD-1, participates in immune regulation \[2\]. Furthermore, sPD-L1 was found to be involved in tumour-associated immune suppression and host immune damage, thereby promoting cancer progression and subsequent adverse clinical out- comes\[3\]. In addition, high level of sPD-L1 maybe also associated with the prognosis of malignancies, including colorectal cancer PD-L1, an immune-regulatory molecule, is highly expressed on tumor cells and can be present on activated T and B cell dendritic cells (4). The activation of the programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) pathway was found as one of the key mechanisms in tumor immune evasion (5). Thus, antibody- based immunotherapies blockading the PD-1/PD-L1 signaling pathways in the tumor microenvironment and stimulating the T-cell anti-tumor activity are a promising approach for developing novel tumor therapeutics in routine clinical practices.