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

Programmed cell death 1 ligand 1 (PD-L1) and ligand 2 (PD-L2) are critical transmembrane proteins that function as immune checkpoint molecules to maintain peripheral tolerance and prevent autoimmunity. In the context of mesenchymal stem cell (MSC) therapy, these ligands are expressed or upregulated on MSCs to suppress the activity of immune effector cells, such as T cells and natural killer (NK) cells, through direct interaction with the PD-1 receptor (Source: UniProt Q9NZQ7). This MSC-mediated signaling, often supported by paracrine factors like indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2), is a primary mechanism for the therapeutic efficacy of MSCs in treating graft-versus-host disease and other inflammatory conditions (Source: PubMed PMID: 28210154). Conversely, many cancers exploit this pathway by overexpressing PD-L1/PD-L2 to create an immunosuppressive microenvironment, allowing tumors to evade immune detection. Therapeutic interventions include monoclonal antibodies that block the PD-1/PD-L1 axis to restore anti-tumor immunity, as well as the development of MSC-based products that utilize this pathway to dampen pathological inflammation (Source: NIH/StatPearls). Understanding the balance of this signaling is vital for both enhancing cancer immunotherapy and developing cell-based treatments for autoimmune diseases.

Other names

CD274CD273B7-H1B7-DCProgrammed death-ligand 1Programmed death-ligand 2PDCD1L1PDCD1L2

PD-L1 and PD-L2 bind to the PD-1 receptor on immune effector cells, leading to the recruitment of the phosphatase SHP-2, which dephosphorylates signaling molecules downstream of the T-cell receptor (TCR), thereby inhibiting T-cell activation and cytokine production (Source: PubMed PMID: 30073234).