Nasopharyngeal carcinoma (NPC) is one of the most common tumors of head and neck in the Southeast Asia. PD-L1-dependent immune escape plays a critical role involved in NPC development. BPIFB1 has previously reported to take tumor-suppressive actions on NPC cell proliferation and migration. Nonetheless, the function of BPIFB1 in immune escape remains largely elusive. Expression pattern on mRNA and protein levels of target genes in NPC patients’ samples and cell lines were examined by qRT-PCR, western blot, and immunohistochemistry staining, respectively. The assessment of CD8⁺ T-cell apoptosis and expression was determined by flow cytometry. Molecular interactions were verified using chromatin immunoprecipitation (ChIP) and luciferase reporter assay. BPIFB1 was downregulated in NPC tumor tissues, exhibiting a negative correlation of PD-L1. Overexpression of BPIFB1 significantly inhibited the expression of PD-L1, suppressing the apoptosis and enhancing the expression of CD8⁺ T cells. Mechanistically, BPIFB1 was found to repress the expression of STAT1, which was identified to be an upstream activator of PD-L1. Furthermore, the EBV-encoded miR-BART4 overexpressed in NPC cells could directly target and inhibit BPIFB1. This study provided a comprehensive understanding of the molecular mechanism for the upstream and downstream pathway of BPIFB1 related with immune escape, indicating a novel approach for the treatment of NPC.

鼻咽癌（NPC）是东南亚最常见的头颈部肿瘤之一。PD-L1 依赖性免疫逃逸在 NPC 发育中发挥着关键作用。BPIFB1 此前曾报道对鼻咽癌细胞增殖和迁移具有肿瘤抑制作用。尽管如此，BPIFB1 在免疫逃逸中的功能仍然很大程度上难以捉摸。分别通过qRT-PCR、蛋白质印迹和免疫组织化学染色检查鼻咽癌患者样本和细胞系中靶基因的mRNA和蛋白水平的表达模式。^{CD8 +} T细胞凋亡和表达的评估通过流式细胞术测定。使用染色质免疫沉淀 (ChIP) 和荧光素酶报告基因测定验证分子相互作用。BPIFB1在鼻咽癌肿瘤组织中表达下调，与PD-L1呈负相关。^{BPIFB1的过表达显着抑制PD-L1的表达，抑制细胞凋亡并增强CD8 +} T细胞的表达。从机制上讲，BPIFB1 可抑制 STAT1 的表达，而 STAT1 被确定为 PD-L1 的上游激活剂。此外，鼻咽癌细胞中过表达的EBV编码的miR-BART4可以直接靶向并抑制BPIFB1。该研究全面了解了BPIFB1上下游通路与免疫逃逸相关的分子机制，为鼻咽癌的治疗提供了新的途径。