Role of the HDAC6/STAT3 pathway in regulating PD-L1 expression in osteosarcoma cell lines
Role of the HDAC6/STAT3 pathway in regulating PD-L1 expression in osteosarcoma cell lines
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DOI：
10.1007/s00280-018-3721-6
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发表时间：
2019-02-01
影响因子：
3
通讯作者：
Zou, Xiaoguang
中科院分区：
文献类型：
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作者：
Keremu, Ajimu;Aimaiti, Abudusaimi;Zou, Xiaoguang
组蛋白去乙酰化酶（HDAC），最初被描述为组蛋白修饰剂，最近已被证实靶向各种其他蛋白质无关的染色质环境。在此基础上，本研究的发现表明，骨肉瘤细胞系中HDAC 6的药理学或遗传学废除下调了程序死亡受体配体-1（PD-L1）的表达，PD-L1是癌细胞中表达的重要共刺激分子，其激活T细胞中的抑制性调节途径PD-1。正如我们的结果所示，HDAC 6调节PD-L1表达的机制是由转录因子STAT 3介导的。此外，我们观察到选择性HDAC 6抑制剂可以抑制体内肿瘤进展。至关重要的是，这些结果为进一步研究HDAC 6抑制剂作为骨肉瘤潜在免疫调节剂的必要性提供了基本的临床前理论基础和理由。
Histone deacetylases (HDACs), initially described as histone modifiers, have more recently been verified to target various other proteins unrelated to the chromatin environment. On this basis, findings of the current study demonstrates that the pharmacological or genetic abrogation of HDAC6 in osteosarcoma cell lines down-regulates the expression of program death receptor ligand-1 (PD-L1), an important co-stimulatory molecule expressed in cancer cells, which activates the inhibitory regulatory pathway PD-1 in T cells. As shown by our results, the mechanism by which HDAC6 regulated PD-L1 expression was mediated by the transcription factor STAT3. In addition, we observed that selective HDAC6 inhibitors could inhibit tumor progression in vivo. Crucially, these results provide an essential pre-clinical rationale and justification for the necessity of further research on HDAC6 inhibitors as potential immuno-modulatory agents in osteosarcoma.