Project description:Analysis of differentially expressed genes in wild type A4573 Ewing Sarcoma cells when compared to A4573 Ewing Sarcoma cells that received six 4 Gy fractions (cumulative dose of 24 Gy) of ionizing radiation (radiation-adapted cell line). The hypothesis tested being that repeated ionizing radiation exposure of modifies radiation therapy response in Ewing Sarcoma.
Project description:Analysis of differentially expressed genes in wild type SK-ES1 Ewing Sarcoma cells when compared to SK-ES1 Ewing Sarcoma cells that received six 4 Gy fractions (cumulative dose of 24 Gy) of ionizing radiation (radiation-adapted cell line). The hypothesis tested being that repeated ionizing radiation exposure of modifies radiation therapy response in Ewing Sarcoma.
Project description:Analysis of differentially expressed genes in wild type MHH-ES-1 Ewing Sarcoma cells when compared to MHH-ES-1 Ewing Sarcoma cells that received six 4 Gy fractions (cumulative dose of 24 Gy) of ionizing radiation (radiation-adapted cell line). The hypothesis tested being that repeated ionizing radiation exposure of modifies radiation therapy response in Ewing Sarcoma.
Project description:Ewing sarcoma is an aggressive cancer most commonly diagnosed in adolescents and young adults. Various mechanisms of TGFβ inhibition are being tested in clinical trials for patients with relapsed Ewing sarcoma. However, the functional impact of TGFβ inhibition on the Ewing tumor microenvironment remains largely unstudied given the historical lack of immunocompetent preclinical models of Ewing sarcoma. Here, we use single cell RNAseq analysis of human Ewing tumors to demonstrate that immune cells are the largest source of TGFβ production in the human Ewing tumor microenvironment. We develop and utilize a humanized mouse model of Ewing sarcoma to study the effect of TGFβ inhibition on the Ewing tumor immune microenvironment both at baseline and during radiation therapy, a treatment that enhances TGFβ activation and is often used to treat patients with aggressive Ewing sarcoma. Finally, we utilize a bivalent ligand TGFβ TRAP and demonstrate that, in combination with radiation, TGFβ inhibition both increases immune cell infiltration in Ewing tumors and decreases lung metastatic burden.
