PD-L1是一种免疫检查点抑制剂，其表面表达可能被癌细胞利用以逃避T细胞介导的免疫识别。PD-L1表达和核定位受到表观遗传修饰的影响，例如乙酰化。在这项研究中，我们展示了类I/IIa HDAC抑制剂VPA通过上调胰腺癌细胞表面的PD-L1表达起作用。这效应是由于PD-L1基因转录的增加与组蛋白乙酰化的相关性，并伴随PD-L1蛋白的乙酰化，从而使其与PD-L1回收到细胞膜中的分子TRAPPC4发生增加的相互作用。有趣的是，BRD4抑制剂JQ-1抵消了PD-L1的转录并降低了其表面表达，表明这种组合可能改善VPA治疗的效果，也因为它增加了VPA的细胞毒性。还要考虑到这种HDAC抑制剂并未上调PD-L2，并且VPA处理的癌细胞上清液没有增加暴露给其的巨噬细胞表面的PD-L1表达。© 2023. Springer Science+Business Media, LLC.

PD-L1 is an immune checkpoint inhibitor, whose surface expression may be exploited by cancer cells to escape T cell-mediated immune recognition. PD-L1 expression and nuclear localization can be affected by epigenetic modifications, such as acetylation. In this study, we showed that VPA, a class I/IIa HDAC inhibitor, upregulated PD-L1 expression on the surface of pancreatic cancer cells. To this effect contributed the increased transcription, in correlation with histone acetylation of the PD-L1 gene and the acetylation of PD-L1 protein, which led to an increased interaction with TRAPPC4, molecule involved in PD-L1 recycling to the cell membrane. Interestingly, the BRD4 inhibitor JQ-1, counteracted PD-L1 transcription and reduced its surface expression, suggesting that such a combination could improve the outcome of VPA treatment, also because it increased the cytotoxic effect of VPA. Also considering that this HDACi did not upregulate PD-L2 and that the supernatant of VPA-treated cancer cells did not increase PD-L1 expression on the surface of macrophages exposed to it.© 2023. Springer Science+Business Media, LLC.