Posttranslational regulatory mechanism of PD-L1 in cancers and associated opportunities for novel small-molecule therapeutics.

Despite the tremendous progress in cancer research over the past few decades, effective therapeutic strategies are still urgently needed. Accumulating evidence suggests that immune checkpoints are the cause of tumor immune escape. PD-1/PD-L1 are among them. Posttranslational modification is the most critical step for protein function, and the regulation of PD-L1 by small molecules through posttranslational modification is highly valuable. In this review, we discuss the mechanisms of tumor cell immune escape and several posttranslational modifications associated with PD-L1 and describe examples in which small molecules can regulate PD-L1 through posttranslational modifications. Herein, we propose that the use of small molecule compounds that act by inhibiting PD-L1 through posttranslational modifications is a promising therapeutic approach with the potential to improve clinical outcomes for cancer patients.