文章：

栓塞后头颈部副神经节瘤中PD-L1与HIF-2α表达上调

PD-L1 and HIF-2α Upregulation in Head and Neck Paragangliomas after Embolization

原文发布日期：29 October 2023

DOI: 10.3390/cancers15215199

类型: Article

开放获取: 是

英文摘要：

Hypoxia activates pathways associated with tumor progression, metastatic spread, and alterations in the immune microenvironment leading to an immunosuppressive phenotype. In particular, the upregulation of PD-L1, a target for therapy with checkpoint inhibitors, is well-studied in several tumors. However, the relationship between hypoxia and PD-L1 regulation in pheochromocytomas and paragangliomas (PPGL), and especially in paragangliomas treated with embolization, is still largely unexplored. We investigated the expression of the hypoxia-marker HIF-2α and of PD-L1 in a PPGL-cohort with and without embolization as potential biomarkers that may predict the response to treatment with HIF-2α and checkpoint inhibitors. A total of 29 tumor samples from 25 patients who were operated at a single center were included and analyzed utilizing immunohistochemistry (IHC) for PD-L1 and HIF-2α. Embolization prior to surgery was performed in seven (24%) tumors. PD-L1 expression in tumor cells of head and neck paragangliomas (HNPGLs) receiving prior embolization (median PD-L1 positivity: 15%) was significantly higher as compared to PD-L1 expression in HNPGLs without prior embolization (median PD-L1 positivity: 0%) (p= 0.008). Consistently, significantly more HNPGLs with prior embolization were positive for HIF-2α (median nuclear HIF-2α positivity: 40%) as compared to HNPGLs without prior embolization (median nuclear HIF-2α positivity: 0%) (p= 0.016). Our results support the hypothesis that embolization with subsequent hypoxia leads to the upregulation of both PD-L1 and HIF-2α in HNPGLs, and could thus facilitate targeted treatment with HIF-2α and checkpoint inhibitors in the case of inoperable, locally advanced, or metastatic disease.

摘要翻译： 

缺氧可激活与肿瘤进展、转移扩散及免疫微环境改变相关的通路，导致免疫抑制表型。特别是在多种肿瘤中，作为检查点抑制剂治疗靶点的PD-L1上调机制已得到充分研究。然而，在嗜铬细胞瘤和副神经节瘤（PPGL）中，尤其是接受过栓塞治疗的副神经节瘤，缺氧与PD-L1调控的关系仍很大程度上未被探索。本研究通过检测PPGL队列（含栓塞与非栓塞病例）中缺氧标志物HIF-2α与PD-L1的表达，探讨其作为预测HIF-2α及检查点抑制剂治疗反应的潜在生物标志物。研究纳入单中心手术治疗的25例患者的29份肿瘤样本，采用免疫组化法检测PD-L1和HIF-2α表达。其中7例（24%）肿瘤在术前接受过栓塞治疗。结果显示：接受过栓塞治疗的头颈部副神经节瘤（HNPGLs）肿瘤细胞中PD-L1表达（中位阳性率15%）显著高于未栓塞组（中位阳性率0%）（p=0.008）；与此一致，栓塞组HIF-2α核阳性率（中位值40%）也显著高于非栓塞组（中位值0%）（p=0.016）。本研究结果支持以下假设：栓塞后继发的缺氧可导致HNPGLs中PD-L1和HIF-2α表达上调，这为无法手术、局部进展或转移性病例进行HIF-2α及检查点抑制剂的靶向治疗提供了理论依据。

原文链接：

PD-L1 and HIF-2α Upregulation in Head and Neck Paragangliomas after Embolization