PD-L2, also known as Programmed Death-Ligand 2 or B7-DC, is a protein encoded by the PDCD1LG2 gene, which is located on chromosome 9p24.2. PD-L2 is one of the two Programmed Death Ligands (PD-L) and a member of the CD28 family of immune receptors. In the human body, PD-L2 is widely expressed in various tissues, including the placenta, heart, pancreas, lungs, and liver, but its expression is relatively low in the spleen, lymph nodes, and thymus. PD-L2 plays multiple roles in the immune system. Firstly, it can bind to PD-1 and inhibit the immune activation of T cells through downstream signaling pathways such as tyrosine phosphatase-2 (SHP-2). Secondly, PD-L2 can also bind to repulsive guidance molecule b (RGMb), activating the bone morphogenetic protein receptor pathway and promoting the functional activation of T cells. This dual functionality makes PD-L2 an important player in immune regulation. Furthermore, PD-L2 plays a significant role in tumor immune evasion mechanisms. It can both activate and inhibit T cells and may contribute to the development of immune-related pneumonia. Some studies have suggested that the expression of PD-L2 is associated with poor prognosis in esophageal cancer, supporting its role as a prognostic biomarker.
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