最近的研究指出了Krüpple-like因子12（KLF12）在癌症相关过程中的作用，包括癌症增殖、凋亡和转移。然而，KLF12在肿瘤免疫中的作用仍不明确。在这里，我们发现KLF12表达在非小细胞肺癌（NSCLC）细胞中的程度与程序性死亡相关配体1（PD-L1）的表达水平显著相关。此外，在临床患者的肿瘤组织中观察到了KLF12与PD-L1之间的正相关。通过染色质免疫沉淀（ChIP）分析，我们确定KLF12能够结合到PD-L1启动子的CACCC序列。KLF12的过表达促进了PD-L1的转录，而KLF12的沉默抑制了PD-L1的转录。此外，当缺乏KLF12时，信号传导子和转录激活物1（STAT1）和STAT3触发的PD-L1转录被抑制，并且KLF12减弱了STAT1和STAT3与PD-L1启动子的结合。机制上，KLF12与组蛋白乙酰转移酶P300发生了物理相互作用。此外，KLF12的沉默减少了P300与PD-L1启动子的结合，进而导致组蛋白H3的乙酰化水平下降。EP300的沉默消除了由KLF12过表达引起的PD-L1转录。在免疫竞争小鼠模型中，KLF12基因敲除抑制了肿瘤生长并促进了CD8+ T细胞的浸润。然而，在免疫缺陷小鼠中未观察到这种现象。总之，本研究揭示了KLF12在NSCLC中调控PD-L1的转录调控机制；靶向KLF12可能是NSCLC的潜在治疗策略。© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Recent studies have pointed to the role of Krüpple-like factor 12 (KLF12) in cancer-associated processes, including cancer proliferation, apoptosis, and metastasis. However, the role of KLF12 in tumor immunity remains obscure. Here, we found that KLF12 expression was significantly higher in non-small cell lung cancer (NSCLC) cells with higher programmed death-ligand 1 (PD-L1) expression. Additionally, a positive correlation between KLF12 and PD-L1 was observed in clinical patient tumor tissues. By chromatin immunoprecipitation (ChIP) analysis, KLF12 was identified to bind to the CACCC motif of the PD-L1 promoter. Overexpression of KLF12 promoted PD-L1 transcription, whereas silencing of KLF12 inhibited PD-L1 transcription. Furthermore, signal transducer and activator of transcription 1 (STAT1)- and STAT3-triggered PD-L1 transcription was abolished in the absence of KLF12, and KLF12 knockdown weakened the binding of STAT1 and STAT3 to the PD-L1 promoter. Mechanistically, KLF12 physically interacted with P300, a histone acetyltransferase. In addition, KLF12 silencing reduced P300 binding to the PD-L1 promoter, which subsequently caused decreased acetylation of histone H3. PD-L1 transcription driven by KLF12 overexpression was eliminated by EP300 silencing. In immunocompetent mice, KLF12 knockout inhibited tumor growth and promoted infiltration of CD8+ T cells. However, this phenomenon was not observed in immunodeficient mice. Overall, this study reveals KLF12-mediated transcriptional regulation of PD-L1 in NSCLC; targeting KLF12 may be a potential therapeutic strategy for NSCLC.© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.