Progress in understanding the regulatory mechanisms of immune checkpoint proteins PD-1 and PD-L1 expression

Clin Transl Oncol. 2025 Jan 8. doi: 10.1007/s12094-024-03835-4. Online ahead of print.

Abstract

Programmed Death Protein-1 (PD-1) is a cell surface receptor that serves as a checkpoint for T cells, playing a pivotal role in regulating T-cell apoptosis. The binding of PD-1 to its ligand, Programmed Death Ligand 1 (PD-L1), inhibits anti-tumor immunity by suppressing T-cell activation signals. Indeed, the PD-1/PD-L1 pathway governs the induction and maintenance of immune tolerance within the tumor microenvironment. Consequently, the regulation of PD-1/PD-L1 immune checkpoint expression is of paramount importance. This review summarizes the mechanisms governing PD1/PD-L1 expression at various stages, including transcription, post-transcription (mRNA processing), and post-translation (protein modifications), as well as immunotherapy targeting PD1/PD-L1, aiming to further explore novel strategies for tumor immunotherapy.

Keywords: PD-L1; PD1; Post-translational modifications; Transcriptional regulation.

Publication types

  • Review