Programmed cell death protein 1 / Programmed death-ligand 1 axis (PD-1 / PD-L1 axis)

The **Programmed cell death protein 1 / Programmed death-ligand 1 axis** (PD-1/PD-L1 axis) is a fundamental immune checkpoint pathway implicated in the regulation of immune responses and the maintenance of peripheral tolerance. **PD-1** is a type I transmembrane receptor expressed on activated T cells, B cells, some myeloid cells, and macrophages. Its major ligand, **PD-L1**, is a type I transmembrane glycoprotein and member of the B7 family, commonly upregulated on tumor cells as well as on antigen-presenting cells and various non-hematopoietic tissues. Upon engagement with PD-L1, PD-1 transduces an inhibitory signal through its ITIM and ITSM motifs, typically involving recruitment of **SHP-1/2** phosphatases, resulting in reduced T-cell activation, suppressed cytokine production, and increased apoptosis of antigen-specific T cells[1][3][6][7]. This suppressive mechanism allows tumors to evade immune detection, which makes the axis a pivotal **therapeutic target in oncology**. PD-1/PD-L1 inhibitors are widely used in cancer immunotherapy, with efficacy linked to PD-L1 expression levels in certain cancers. However, blockade of this axis can cause immune-mediated adverse events due to increased immune activation[5][7][8].

Other names

PD-1/PD-L1 pathwayProgrammed cell death protein 1 (PD-1)Programmed death-ligand 1 (PD-L1)CD279 (for PD-1)CD274 (for PD-L1)B7-H1 (for PD-L1)B7 homolog 1 (another for PD-L1)Cluster of differentiation 274 (for PD-L1)PD-L1/PD-1 immune checkpoint axis

Blockade of PD-1/PD-L1 interaction relieves inhibitory signaling in T cells, enhancing anti-tumor immunity; Prevention of PD-1-mediated T cell inactivation by inhibiting ligand-receptor binding; Restoration of cytotoxic T cell activity against tumor cells