2026-04-29T12:24:11Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/230982024-11-30T01:22:54Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud author Fischer, Alessa author Maccio, Umberto author Wang, Katharina author Friemel, Juliane author Broglie Daeppen, Martina A author Vetter, Diana author Lehmann, Kuno author Reul, Astrid author Robledo Batanero, Mercedes author Hantel, Constanze author Bechmann, Nicole author Pacak, Karel author Zitzmann, Kathrin author Auernhammer, Christoph J author Grossman, Ashley B author Beuschlein, Felix author Nölting, Svenja 2024-09-16T08:17:02Z 2024-09-16T08:17:02Z 2023-10-29 Cancers (Basel) . 2023 ;15(21):5199. 10.3390/cancers15215199 2072-6694 Cancers 37958373 https://hdl.handle.net/20.500.12105/23098 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-2? and of PD-L1 in a PPGL-cohort with and without embolization as potential biomarkers that may predict the response to treatment with HIF-2? 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-2?. 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-2? (median nuclear HIF-2? positivity: 40%) as compared to HNPGLs without prior embolization (median nuclear HIF-2? 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-2? in HNPGLs, and could thus facilitate targeted treatment with HIF-2? and checkpoint inhibitors in the case of inoperable, locally advanced, or metastatic disease. eng PD-L1 and HIF-2? Upregulation in Head and Neck Paragangliomas after Embolization. research article