ESTRO 2024 - Abstract Book

S5180

Radiobiology - Immuno-radiobiology

ESTRO 2024

Conclusion:

RT combined with icaritin ignite anti-tumor immunity through promoting IFNγ + CD8 + cytotoxic T lymphocytes. Combined therapy may have potential for enhanced tumor control in clinics.

Keywords: tumor microenvironment, cytotoxic T cell

1839

Digital Poster

Stimulation of immune response to overcome radioresistance in BRCA1 mutant breast cancer cells

Sandra Classen 1 , Nadiyya F Zhafirah 1 , Simon Gehre 2 , Michael Rückert 2 , Helmut Pospiech 3,4,5 , Kai Rothkamm 1 , Udo S Gaipl 2 , Cordula Petersen 6 , Kerstin Borgmann 1 1 University Medical Center Hamburg-Eppendorf, Laboratory for Radiobiology and Experimental Radiooncology, Hamburg, Germany. 2 Universitätsklinikum Erlangen, Translational Radiobiology, Department of Radiation Oncology, Erlangen, Germany. 3 Leibniz Institute on Aging - Fritz Lipmann Institute, Project Group Biochemistry, Jena, Germany. 4 University of Oulu, Faculty of Biochemistry and Molecular Medicine, Oulu, Finland. 5 University Hospital Düsseldorf, Research laboratory of the Clinic for Gynecology and Ostetrics, Düsseldorf, Germany. 6 University Medical Center Hamburg-Eppendorf, Department of Radiotherapy and Radiation Oncology, Hamburg, Germany

Purpose/Objective:

Immunotherapy is an evolving area of research and is also being tested in breast cancer (BC). However, current BC trials show only limited benefit for these patients. A better understanding of molecular interactions with other therapies such as radiotherapy is therefore urgently needed. An association of irradiation with activated intracellular immune signaling pathways like cGAS/STING has already been observed. Additionally, a connection to DNA repair processes, especially homologous recombination, and DNA replication stress is being proposed by a number of studies. It is unclear to what extent the interplay of cellular immune response and DNA repair affects radiosensitivity in cells with BRCA1 mutations and is thus the aim of this study.

Material/Methods:

Isogenic BRCA1 mutated MCF7 and MDA-MB-231 BC cell lines with different sensitivities to irradiation (IR) were used. The micronuclei formation and IRF3 translocation was analyzed by immunofluorescence microscopy. Cytosolic DNA was measured using the PicoGreen Assay. Protein expression of cGAS/STING proteins was investigated by Western blot. The immune phenotype was analyzed via the expression of cell surface markers by multicolor flow cytometry. Changes in the secreted chemo- and cytokines were measured by Proteome Profiler Kit and qPCR. The effect of IFNß1 stimulation on cellular survival was analyzed by colony formation assay, DNA repair capacity by 53BP1, yH2AX and Rad51 foci formation and the effect on replication by the DNA fiber assay.

Results: