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Programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) are closely related, structurally homologous cell-surface glycoproteins in the B7 family. They are expressed on a variety of cells, including antigen-presenting cells (APCs), tumor cells, and in peripheral tissues. Both ligands bind the inhibitory receptor PD-1 on T cells, transmitting negative signals that suppress T cell activation and effector functions, thereby promoting immune tolerance or escape. PD-L1 is often more widely expressed and is the dominant ligand in tumors, while PD-L2 has higher binding affinity and distinct expression patterns. Therapeutically, targeting the PD-1/PD-L1/PD-L2 axis unleashes antitumor immunity but may lead to immune-related toxicity. Expression levels of PD-L1 (and, less commonly PD-L2) serve as biomarkers for patient selection in immunotherapy.
Immune checkpoint blockade: drugs bind PD-1, PD-L1, or PD-L2 to block their interaction, *preventing inhibitory signaling*, thus restoring T cell function and anti-tumor immunity
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