PD-L1 regulation revisited: impact on immunotherapeutic strategies

A particularly promising cancer treatment is the use of monoclonal antibodies (mAbs) against immune checkpoints (i.e., immune checkpoint inhibitors; ICIs). However, many patients experience relapse and severe adverse events. To overcome these negative issues and improve efficiency, current approaches rely on combinatorial treatments, including some modulating the expression of programmed cell death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoints directly. In this review, we examine the recently discovered pathways involved in PD-L1 expression and highlight the relevant druggable strategies that are being developed to both improve the response rate and avoid the onset of resistance. Altogether, these new strategies will pave the way for effective treatment combinations in future oncology clinical trials.