文章：

早期生长反应蛋白1作为结外NK/T细胞淋巴瘤中PD-L1表达和免疫逃逸的关键调控因子

Early growth response 1 as a key regulator of PD-L1 expression and immune evasion in extranodal NK/T-cell lymphoma

原文发布日期：2025-06-13

DOI: 10.1038/s41408-025-01313-w

类型: Article

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英文摘要：

This study investigates the role of Early Growth Response 1 (EGR1) in extranodal natural killer/T-cell lymphoma (ENKTL) and its correlation with PD-L1 expression. Analysis of 62 ENKTL patient samples revealed that high EGR1 expression was linked to PD-L1 positivity, the immune evasion-A subtype, and early-stage disease. Although EGR1 expression was not an independent prognostic factor for overall survival, patients with higher EGR1 levels showed a trend toward better outcomes. In ENKTL cell lines (YT, SNK6), EGR1 positively regulated LMP1 and PD-L1 expression. Knockdown of EGR1 reduced PD-L1 levels, decreased PTEN, increased AKT phosphorylation, and abrogated STAT3 phosphorylation. Conversely, EGR1 overexpression enhanced PD-L1. Treatment with the histone deacetylase inhibitor entinostat upregulated both EGR1 and PD-L1, but this effect was lost in EGR1-depleted cells, indicating EGR1’s necessity for HDAC inhibitor–induced PD-L1 expression. These findings reveal EGR1’s pivotal role in tumor immune modulation and highlight potential combination therapies targeting EGR1, epigenetic regulators, and PD-1/PD-L1 checkpoints.
 

摘要翻译： 

本研究探讨早期生长反应蛋白1（EGR1）在结外自然杀伤/T细胞淋巴瘤（ENKTL）中的作用及其与PD-L1表达的相关性。通过对62例ENKTL患者样本的分析发现，高EGR1表达与PD-L1阳性、免疫逃逸-A亚型及早期疾病阶段相关。尽管EGR1表达并非总生存期的独立预后因素，但EGR1水平较高的患者显示出更好的预后趋势。在ENKTL细胞系（YT、SNK6）中，EGR1正向调控LMP1和PD-L1表达。敲低EGR1可降低PD-L1水平、减少PTEN表达、增加AKT磷酸化并消除STAT3磷酸化。反之，EGR1过表达则能增强PD-L1表达。组蛋白去乙酰化酶抑制剂恩替司他治疗可同时上调EGR1和PD-L1，但在EGR1缺失的细胞中该效应消失，表明EGR1是HDAC抑制剂诱导PD-L1表达的必要条件。这些发现揭示了EGR1在肿瘤免疫调节中的关键作用，并为针对EGR1、表观遗传调控因子及PD-1/PD-L1检查点的联合疗法提供了潜在方向。

原文链接：

Early growth response 1 as a key regulator of PD-L1 expression and immune evasion in extranodal NK/T-cell lymphoma