ESTRO 2021 Abstract Book

S591

ESTRO 2021

Conclusion In conclusion, the functional profile retrieved from GSEA indicates that immune and DNA biological signatures are associated with radiotherapy-induced late toxicity.

PD-0760 Radiation induced heart fibrosis: Radiation mediated interplay between macrophages and fibroblasts Q. Huang 1,2 , J. Kraske 1,2 , F. Glatting 1,2 , L. Li 1,2 , T. Walle 1 , B. Zou 1,2 , A. Tietz-Dalfuß 1 , S. Trinh 1,2 , D. Albrecht 1 , R. Lopez Perez 1,2 , P. Huber 1,3 1 German Cancer Research Center (DKFZ), Molecular and Radiation Oncology, Heidelberg, Germany; 2 University Hospital Heidelberg, Radiation Oncology, Heidelberg, Germany; 3 University Hospital Heidelberg, Radiation Oncology, Heidelberg, Germany Purpose or Objective Radiotherapy for cancer of organs in the thorax including lung cancer, breast cancer or Hodgkin’s disease can lead to unwanted irradiation of the heart. Because the heart in general is considered relatively radioresistant, the symptoms of radiotherapy-induced heart disease (RIHD) such as fibrosis may require decades to manifest. However RIHD is becoming more important due to the increasing cancer patient survival, and RIHD may substantially contribute to the causes of death in these cancer survivors. Despite the many clinical data, preclinical and cell mechanistic investigations are sparse. Therefore, here we hypothesized that the interplay of immune cells with cardiac fibroblasts play a role in radiation induced cardiac fibrogenesis, and analyzed in vitro the TGFß, PDGF, and CTGF related signaling program including senescence potentially playing a role in this process. Materials and Methods To this end we established a radiation induced primary human cardiac fibroblast (HCF) - human macrophage (from PBMC monocytes) activation model, measured proliferation, senescence (ß-gal), clonogenic survival, analyzed protein expression by Western blot and ELISA, and transcriptomic changes in the cells alone and in coculture with and without specific small molecule inhibitors of PDGF and TGFß signaling (Sunitinib/Galunisertib analogues). Results We found that radiation upregulated profibrotic genes including αSMA, Col 1a1, Cola 3a1, Col 4a1, Col 5a1, TGFß1, CTGF, chemokines such as IL6 and senescence markers in HCF on the mRNA or the protein level. The