Mechanisms of PD-L1 Regulation in Tumor Immune Ecosystem

PD-1 (Programmed Death Receptor-1) is a cell membrane protein found on Cytotoxic T cells (CTLs) surface. An abundantly expressed type I transmembrane protein in healthy tissues, Programmed Death-Ligand 1 (PD-L1), has a molecular mass of 40 kDa. The extracellular binding of the proteins PD-1 and PD-L1 prevents the development of autoimmune disorders by suppressing the activation of CTLs under normal physiological conditions. It has been shown that cancer cells can avoid immune monitoring by increasing PD-1/PD-1-mediated CTL inactivation in melanoma, lung cancer, renal cell carcinoma, and other malignant tumors. PD-L1 expression regulation has been described in recent years from the standpoint of gene amplification, chromatin modification, post-transcription and transcription modification, translation, and post-translational modification. Anti-PD-1 immunotherapy has demonstrated promising results in treating several cancers, including breast, lung, and prostate cancers. This review aims to present the most recent research findings in PD-L1 regulation in cancer cells. A tumor immunotherapy strategy targeting PD-1 and PD-L1 is expected to be useful.