Programmed death-ligand 1 and Programmed death-ligand 2 (PD-L1 and PD-L2)

Programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) are both members of the B7 protein family and serve as ligands for programmed cell death protein 1 (PD-1), an immunoinhibitory receptor widely expressed on lymphocytes[6][2][3]. PD-L1 is broadly expressed on hematopoietic and nonhematopoietic cells, while PD-L2 has a more restricted pattern, mainly on antigen-presenting cells[2][4]. Both molecules function as key immune checkpoint regulators: by binding PD-1, they suppress T-cell activation, proliferation, and cytokine production, maintaining peripheral tolerance and controlling immune responses, especially during pregnancy, infection, autoimmune reactions, and cancer[6][3][1]. In cancer, upregulation of PD-L1 and/or PD-L2 allows malignant cells to evade anti-tumor immunity, a process exploited therapeutically by monoclonal antibodies that disrupt these interactions[3][4][6]. PD-L2 binds PD-1 with higher affinity than PD-L1 and may have distinct regulatory and activating effects on dendritic cells[1][2][4]. Both proteins are now targets for immunotherapy and are also being explored as biomarkers and for combination therapeutic strategies. Notable safety concerns arise due to loss of immune tolerance with checkpoint blockade, resulting in immune-related adverse events involving multiple organ systems[4][6].

Other names

CD274B7-H1CD273B7-DC

Checkpoint inhibition: Antibodies block PD-1/PD-L1 or PD-1/PD-L2 interaction, restoring T-cell activation and enabling anti-tumor immune responses. Reactivation of exhausted T cells. Enhancement of cytotoxic T lymphocyte function by preventing inhibitory signaling.