ANP32A negatively regulates PD-L1 expression by acting as the inhibitor of histone acetylase in non-small cell lung cancer

In recent years, immunotherapies with checkpoint inhibitor programmed death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) antibodies have offered a promising new approach to advanced non-small cell lung cancer (NSCLC). Although many NSCLC patients have shown a long-term and lasting response, the high number of non-responders prevents these agents from being used practically. This means that further investigation of PD-L1 regulatory mechanisms and reliable biomarkers to predict the efficacy of anti-PD-1/PD-L1 therapy is still required. The present study demonstrated that low expression of acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) led to a significant enhancement of their migratory and proliferative capacity of lung cancer cells, and was associated with poor prognosis in lung cancer patients. More importantly, we also found that ANP32A was involved in the regulation of PD-L1 expression in lung cancer cells. According to a previous study, ANP32A is the key subunit of the inhibitor of histone acetyltransferase (INHAT) complex. Further mechanistic exploration revealed that low ANP32A could no longer suppress the effect of histone acetyltransferase (HAT), and then the transcriptional activity of the common HAT EP300/CREBBP was enhanced. Subsequently, highly expressed EP300/CREBBP promoted PD-L1 transcription via upgrading histone acetylation of the PD-L1 promoter region on the histone H3 lysine 27 acetylation site. Therefore, ANP32A, as an important factor for predicting lung cancer prognosis and regulating PD-L1 expression, deserves more attention and exploration.