Abstract
Immune checkpoint therapy, such as the reactivation of T-cell activity by targeting programmed cell death 1 (PD-1) and its ligand PD-L1 (also called B7-H1 and CD274) has been found pivotal in changing the historically dim prognoses of malignant tumors by causing durable objective responses. However, the response rate of immune checkpoint therapy required huge improvements. It has been shown that the expression of PD-L1 on cancer cells and immune cell membranes is correlated with a more durable objective response rate to PD-L1 antibodies, which highlights the importance of deeply understanding how this protein is regulated. Posttranslational modifications such as phosphorylation, N-glycosylation, and ubiquitination of PD-L1 have emerged as important regulatory mechanisms that modulate immunosuppression in patients with cancer. In this review, we summarized the latest findings of PD-L1 protein modification and their clinical applications.
Highlights
Immune checkpoints are the molecules that negatively regulate the activity of T cells
posttranslational modifications (PTMs) such as phosphorylation, N-glycosylation, ubiquitination, and palmitoylation of programmed death ligand 1 (PD-L1) have been approved to be very important for immunotherapy
Given that PTMs are often therapeutic targets for pharmacologic inhibition of cancer, a better understanding of the PTMs of PD-L1 in malignant tumors is of utmost importance
Summary
Immune checkpoints are the molecules that negatively regulate the activity of T cells. By targeting checkpoints such as programmed cell death 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1), has shown an important clinical benefit, which has placed tumor immunotherapy in the spotlight [1]. Finding of effective biomarkers that could identify patients who would be benefitted is crucial, to increase treatment efficacy and to reduce the risk of those estimated to be unresponsive patients from the side effects of immunotherapy. Identifying these unresponsive patients would be the first milestone to achieve for developing new drugs to overcome immune checkpoint block resistance [6]. We summarized the latest findings in the most important PTMs of PD-L1 protein, including N-glycosylation, phosphorylation, ubiquitination, and palmitoylation (Figure 1)
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