Research Progress on Regulation Mechanism of PD-L1 Expression in Cancer Cells

Cell surface receptor PD-1 (programmed death receptor-1) anchors on the cell membrane of antigen-specific CTLs (cytotoxic T lymphocytes). PD-1 binds to its ligand PD-L1 (programmed death-ligand 1), which is a type I transmembrane protein. PD-L1 is widely expressed in normal tissues with a molecular weight of about 40 kDa. Extracellular binding between PD-1 and PD-L1 inhibits the activity of CTLs and prevents autoimmunity under normal physiological conditions. However, the aberrantly upregulated expression of PD-L1 in malignant tumors such as melanoma, lung cancer, and renal cell carcinoma facilitates PD-1/PD-L1-mediated CTLs deactivation and leads to the immune evasion of cancer cells. In recent years, molecular mechanisms that modulating PDL1 expression from the views of gene amplification, chromatin modification, transcription and post-transcriptional modification, translation and post-translational modification have been unraveled. Meanwhile, immune checkpoint blockade targeting PD-1/PD-L1 axis has exhibited promise in the clinical treatment of a variety of malignancies. In this review, the academic achievements in the regulatory pathways of PD-L1 in cancer cells are summarized, and the perspectives of tumor immunotherapy targeting the PD-1/PD-L1 axis are prospected.

CSTR: 32200.14.cjcb.2021.12.0017