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

The Programmed cell death protein 1 (PD-1) and Programmed death-ligand 1 (PD-L1) interface is a critical immune checkpoint axis that maintains peripheral tolerance and prevents autoimmunity [2, 3]. PD-1 is an inhibitory receptor expressed on activated T cells, while PD-L1 is a ligand often overexpressed by tumor cells to evade immune detection [7, 12]. When PD-L1 binds to PD-1, it triggers inhibitory signaling that suppresses T-cell proliferation, cytokine production, and cytotoxic activity, effectively leading to T-cell exhaustion [5, 9]. In the context of oncology, this interaction allows tumors to escape the host's immune surveillance and continue proliferating [1, 11]. Therapeutic agents, primarily monoclonal antibodies, target this interface by blocking either PD-1 or PD-L1, thereby restoring the anti-tumor activity of the immune system [6, 13]. This approach has become a cornerstone of modern cancer therapy, showing efficacy in numerous malignancies such as melanoma and lung cancer [4, 10]. However, disrupting this pathway can also lead to immune-related adverse events (irAEs) as the immune system may attack healthy tissues [14].

Other names

PD-1/PD-L1 axisPD-1/PD-L1 pathwayPD-1/B7-H1 interactionPD-1/CD274 interactionImmune checkpoint PD-1/PD-L1

Immune checkpoint inhibition; blocking the interaction between PD-1 and PD-L1 to prevent co-inhibitory signaling and restore T-cell mediated anti-tumor immunity [2, 9, 12].