Role of β-catenin in PD-L1 expression of nasopharyngeal carcinoma

β-catenin在鼻咽癌PD-L1表达中的作用

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作者:Haihua Wang, Kaiju Luo, Yuting Zhan, Shuping Peng, Songqing Fan, Weiyuan Wang

Abstract

Nasopharyngeal carcinoma (NPC) is a particular type of tumor connected to Epstein-Barr virus infection, genetic, and environmental factors. It is typically discovered late, with few therapeutic options and poor clinical outcomes. Cellular immune responses can be attenuated when programmed death ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) are combined. Although PD-1 inhibitors have a different anti-tumor response rate than chemotherapy alone, they can nevertheless considerably outperform chemotherapy in patients with metastatic or recurrent NPC. The nuclear β-catenin can bind to the CD274 promoter region, promoting transcription and upregulating the expression of tumor-specific PD-L1. Separation of β-catenin from E-cadherin and translocation it into nucleus were both aided by β-catenin phosphorylates at the Tyr654 site. Its function in NPC and the expression of PD-L1 have not yet been investigated. This study investigated the predictive significance of PD-L1 and p-β-cateninTyr654 expressions in NPC. Our findings indicated that patients with distant metastases or poor prognoses exhibited higher levels of PD-L1 and p-β-cateninTyr654 expressions. According to Cox multivariate prognostic analysis, PD-L1 was also an effective indicator for predicting the survival status of patients with NPC. We subsequently demonstrated that PD-L1 transcription and protein production could be downregulated by targeting inhibition of the level of β-catenin in NPC cells. This is for developing the β-catenin or TCF4 inhibitor as a potential new option for immune checkpoint immunosuppression in NPC.

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