Immunotherapy presents promising results for cancer treatment in the past few years. PD-1, also known as CD279, is a 55-kDa transmembrane protein containing 288 amino acids. First discovered in 1992, PD-1 served as an inhibitor of both innate and adaptive immune responses. Of note, PD-1 is highly expressed on tumor-specific T cells.
PD-L1, also known as CD279 and B7-H1, is a 33-kDa type 1 transmembrane glycoprotein that contains 290 amino acids. Usually expressed by macrophages, activated T cells, and activated B cells, PD-L1 acts as a pro-tumorigenic factor via binding to its receptors and activating proliferative and survival signaling pathways in cancer cells. PD-L2 is the other ligand for PD-1 to activate pathways inhibiting TCR/BCR-mediated immune cell activation. PD-L2 is primarily expressed on professional antigen-presenting cells, including dendritic cells (DCs) and macrophages. The expression of PD-1/PD-L1 can be modulated by various signals, such as PI3K/AKT pathway, MAPK pathway, JAK/STAT pathway, WNT pathway, NF-κB pathway, and Hedgehog (Hh) pathway.
Recent research has shown that PD-1 and PD-L1/PD-L2 pathway plays important roles in various cancers, including breast cancer, lung cancer, colorectal cancer, gastric cancer, bladder cancer, pancreatic cancer, and prostate cancer. In this case, inhibitors targeting PD-1/PD-L1 have been reported for cancer therapy, and some of them are approved. In summary, PD-1 and PD-L1/PD-L2 pathway is an opportunity and challenge for cancer treatment. As a promising treatment, immunotherapy may lead to further survival for patients and a number of problems that need to be solved.
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