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bioRxiv · 10.1101/2025.01.31.635996

Tumor-associated stroma shapes the spatial tumor immune microenvironment of primary Ewing sarcomas

Kuo, C.·Giannikou, K.·Wang, N.·Warren, M.·Goodspeed, A.·Shillingford, N.·Hayashi, M.·Raredon, M. S. B.·Amatruda, J.
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Abstract

To date, few studies have detailed the tumor microenvironment (TME) of Ewing sarcoma (EwS). The TME has a vital role in cancer survival and progression with implications in drug resistance and immune escape. By performing spatially resolved transcriptomic analysis of primary treatment-naive EwS samples, we discovered greater stromal enrichment in localized EwS tumors compared to metastatic EwS tumors. Through spatial ligand-receptor analysis, we show that the stromal enriched regions harbor unique extracellular matrix related cytokines, immune recruitment and proinflammatory microenvironmental signals, implying EwS stroma may play an anti-tumorigenic role by acting as an immune recruitment center. All EwS tumors expressed pro-tumorigenic MIF-CD74 immune signaling, suggesting a potential immune-evasive mechanism and immunotherapy target. Our findings provide insight into tumor cell/stromal cell interactions in EwS and serve as a valuable resource for further investigations in the tumor immune microenvironment of EwS.

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Kuo, C., Giannikou, K., Wang, N., Warren, M., Goodspeed, A., Shillingford, N., Hayashi, M., Raredon, M. S. B., Amatruda, J.. 2025-02-06. Tumor-associated stroma shapes the spatial tumor immune microenvironment of primary Ewing sarcomas. https://doi.org/10.1101/2025.01.31.635996

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