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.
Fig.1 PD-1/PD-L1 axis inhibits T cell activation, proliferation, and survival, and cytotoxic secretion within cancer cells. (Han, 2020)
Research and Drugs for PD-1 and PD-L1/PD-L2 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, prostate cancer, and DLBCL tumor. In this case, inhibitors targeting PD-1/PD-L1 have been reported for cancer therapy, and some of them are approved by FDA. 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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