Landscape of PD-1/PD-L1 Regulation and Targeted Immunotherapy

Abstract

Programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) is a significant immune checkpoint, and the dysfunction of this axis contributes to tumor metastasis and immune escape. PI3K/Akt/mTOR and MAPK signal network induces PD-1/PD-L1 expression and facilitates tumor progression. Transcriptional factors such as hypoxia induced factors, PTEN, p53, CDK5, BRD4, STAT modulate PD-1/PDL1 expression. PD-1/PD-L1 level is also regulated via epigenetic and post-translational manner. The underlying mechanisms mentioned above may provide potential targets for tumor treatment. At present, the combination therapy of PD-1/PD-L1 monoclonal antibodies plus small molecular inhibitors has achieved good outcomes in tumor treatment.