以PD-L1为靶点的免疫疗法在抗肿瘤、抗感染及抗自身免疫性疾病等方面均具有重要意义。研究表明，CDK5缺失导致PD-L1的表达降低，而在CDK5缺失的肿瘤中IRF2BP2呈现高度磷酸化。而且我们此前的研究发现：在非小细胞肺癌中，VGLL4的缺失会影响IRF2BP2的蛋白稳定性，进而促进IRF2与PD-L1启动子的结合，抑制IRF1与PD-L1启动子的结合，抑制PD-L1的表达。为深入理解IRF2BP2磷酸化对IRF1活性及PD-L1表达的调控，我们筛选并得到了能够磷酸化IRF2BP2的激酶NLK，并进行了初步研究。本研究将综合运用小鼠模型、生化细胞等手段阐明NLK在IRF2BP2调控PD-L1的表达过程中发挥的作用，以期为非小细胞肺癌等相关疾病的治疗提供理论依据和治疗策略。

A major feature of immune evasion in cancer cells is the expression of multiple inhibitory ligands on the surface, such as PD-L1. Therefore, it is important to identify new factors regulate PD-L1 level in cancer cells. It has been reported that the expression of PD-L1 is decreased and IRF2BP2 is highly phosphorylated in CDK5-deficient tumors. Moreover, our previous studies showed that deficient of VGLL4 in non-small cell lung cancer cells decreased the protein stability of IRF2BP2, which promotes the binding of IRF2 to the PD-L1 promoter, inhibits the binding of IRF1 to the PD-L1 promoter, and inhibits the expression of PD-L1. In order to gain a further understanding of the regulation of IRF1 and PD-L1 by IRF2BP2 phosphorylation, we identified that NLK is capable of phosphorylating IRF2BP2. In this study we will use syngeneic mouse models and biochemical technology to elucidate the specific mechanism of IRF2BP2 phosphorylated by NLK to regulate PD-L1, and provide theoretical basis for the treatment of non-small cell lung cancer and other related diseases.