ECEESPE2025 Oral Communications Oral Communications 9: Endocrine Related Cancer (5 abstracts)
Cellular tumor microenvironment cross-talk in pediatric adrenocortical tumors: insights from single-nucleus RNA sequencing
Victoria Fincke 1 , Maurice Loßner 1 , Marina Kunstreich 1 , Irmengard Sax 2 , Marlena Mucha 1 , Felix Dorn 1 , Stefan Wudy 3 , Christian Vokuhl 4 , Christoph Slavetinsky 5 , Jörg Fuchs 6 , Michael Frühwald 1 , Matthias Schlesner 2 , Antje Redlich 7 , Rainer Claus 1 , Michaela Kuhlen 1 & Pascal Johann 1
1University of Augsburg, Pediatrics and Adolescent Medicine, Augsburg, Germany; 2Faculty of Applied Computer Sciences, University of Augsburg, Augsburg, Germany; 3Justus Liebig University Giessen, Giessen, Germany; 4University Hospital Bonn, Bonn, Germany; 5University Children´s Hospital Tuebingen, Tuebingen, Germany; 6University Children´s Hospital Tuebingen, Tübingen, Germany; 7Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
JOINT2138
Pediatric adrenocortical tumors (pACTs) are rare adrenal cortex neoplasms, often presenting with Cushing’s syndrome, virilization, or both. These tumors range from benign pediatric adrenocortical adenomas (pACAs) to aggressive pediatric adrenocortical carcinomas (pACCs). Our prior research identified four DNA methylation-based risk groups correlating with survival outcomes, yet their tumor microenvironment characteristics remain poorly understood. We performed single-nucleus RNA sequencing on 29 pACT samples to characterize immune infiltration and cell-cell communication across these risk groups. Cellular identities were determined using clustering and marker gene expression analysis. Low Risk 1 tumors exhibited significantly greater lymphoid (8.72%) and macrophage (19.75%) infiltration than High Risk tumors (lymphoid: 0.41%; macrophage: 3.6%), suggesting a more active immune environment in lower-risk tumors. Ligand-receptor analysis revealed distinct cell signaling patterns. High Risk tumors demonstrated increased fibroblast-to-endothelial signaling, particularly through collagen-related pathways (COL1A1, COL1A2, COL3A1-ITGA10_ITGB1), indicative of extracellular matrix remodeling and a pro-tumorigenic microenvironment. The MMRN2-CLEC14A interaction emerged as a dominant signal in High Risk tumors, suggesting increased endothelial activation and angiogenesis potential. In contrast, Low Risk 1 tumors showed homeostatic endothelial-fibroblast interactions, with COL1A2-CD93 and COL1A1-CD93 signaling likely contributing to extracellular matrix stabilization and tissue integrity. Notably, immune infiltration and cellular signaling patterns correlated more strongly with DNA methylation-based risk groups than with clinical manifestations such as Cushing’s syndrome or virilization, emphasizing the limitations of clinical features in predicting tumor biology. These findings reveal distinct tumor microenvironment landscapes across pACT risk groups, with High Risk tumors exhibiting a pro-tumorigenic, angiogenic profile, while Low Risk tumors maintain a structured, immune-active microenvironment. The identification of key signaling pathways, such as MMRN2-CLEC14A, suggests potential targets for future therapeutic interventions. Our study underscores the importance of molecular profiling in risk stratification and treatment planning for pediatric adrenocortical tumors.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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