TGFβ Inhibition during Radiotherapy Enhances Immune Cell Infiltration and Decreases Metastases in Ewing Sarcoma.

ABSTRACT: Ewing sarcoma is an aggressive cancer diagnosed in adolescents and young adults. Inhibition of TGFβ is being tested in limited clinical trials for relapsed Ewing sarcoma. TGFβ is an immunosuppressive cytokine that exists in latent and active states. The functional impact of TGFβ inhibition on the Ewing tumor microenvironment (TME) and on Ewing tumor behavior remains largely unknown. In this study, we use single-cell RNA sequencing analysis of human Ewing tumors to demonstrate that immune cells are the largest contributors of TGFB1 expression in the human Ewing TME. We utilize a humanized mouse model of Ewing sarcoma to demonstrate that TME signatures in these models differ significantly from Ewing sarcoma tumors developed in immunodeficient mice. Using this humanized model, we investigate

SUBMITTER: Daley JD 

PROVIDER: S-EPMC12380665 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature