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

Programmed cell death 1 ligand 1 (PD-L1) and Programmed cell death 1 ligand 2 (PD-L2) are type I transmembrane glycoproteins that serve as the primary ligands for the Programmed cell death 1 (PD-1) receptor [1.2.1, 1.4.1]. These proteins are members of the B7 family and are expressed on the surface of various cells, including antigen-presenting cells and, significantly, many types of tumor cells and tumor-associated immune cells [1.1.2, 1.4.5]. The interaction between these ligands and PD-1 on activated T cells delivers a potent inhibitory signal that suppresses T-cell proliferation, cytokine production, and cytotoxic effector functions, thereby maintaining peripheral tolerance and preventing autoimmunity [1.2.1, 1.4.1]. In the context of cancer, tumors exploit this pathway to create an immunosuppressive microenvironment, allowing them to evade immune surveillance and progress [1.1.1, 1.4.4]. Therapeutic strategies targeting the PD-1/PD-L1/PD-L2 axis, primarily through monoclonal antibodies, have revolutionized oncology by restoring anti-tumor immunity across a wide range of malignancies, including non-small cell lung cancer, melanoma, and renal cell carcinoma [1.1.1, 1.3.2]. While highly effective, these therapies can lead to immune-related adverse events (irAEs) due to the systemic disruption of immune checkpoints [1.3.4, 1.3.5].

Other names

CD274B7-H1PDCD1L1PDCD1LG1CD273B7-DCPDCD1L2PDCD1LG2

Monoclonal antibodies bind to PD-L1, preventing its interaction with the PD-1 receptor on T cells, thereby restoring anti-tumor immune activity. While most approved drugs specifically target PD-L1, they effectively disrupt the PD-1/PD-L1 signaling axis which is the primary pathway for tumor immune evasion.