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

The Programmed cell death protein 1 (PD-1) and Programmed cell death 1 ligand 1 (PD-L1) axis is a critical immune checkpoint pathway that regulates the balance between immune activation and self-tolerance. PD-1 (CD279) is an inhibitory receptor expressed on the surface of activated T cells, B cells, and Cytokine-Induced Killer (CIK) cells, while its ligand, PD-L1 (CD274), is often upregulated on tumor cells and antigen-presenting cells (UniProt Q15116, Q9NZQ7). The binding of PD-L1 to PD-1 initiates an inhibitory signal that suppresses T-cell proliferation, cytokine release, and cytotoxic activity, facilitating tumor immune evasion (PubMed 31019118). In adoptive cell therapies involving T or CIK cells, the expression of PD-1 can lead to cellular exhaustion and diminished anti-tumor efficacy upon contact with PD-L1-expressing tumors (PubMed 28648221). Therapeutic antibodies targeting this axis block the interaction between PD-1 and PD-L1, thereby restoring the effector functions of T cells and CIK cells against cancer. This pathway is a major focus of cancer immunotherapy, with several approved drugs demonstrating efficacy across multiple tumor types. However, treatment can lead to immune-related adverse events due to the loss of peripheral tolerance. The axis remains a primary target for combination therapies aimed at overcoming resistance in the tumor microenvironment.

Other names

PDCD1/CD274 axisPD-1/PD-L1 pathwayCD279/CD274 axisB7-H1/PD-1 pathwayPD-1 – PD-L1 axis on T/CIK and tumor cells

Blockade of the PD-1/PD-L1 inhibitory interaction to restore T-cell and CIK cell-mediated anti-tumor immunity.