ESTRO 2024 - Abstract Book

S5181

Radiobiology - Immuno-radiobiology

ESTRO 2024

Radiosensitivity was associated with a significant higher activation of the cGAS/STING pathway after IR in the analyzed cell lines. This was shown by a significant increase in cytosolic DNA (p ≤ 0.05), IRF3 translocation from the cytoplasm into the nucleus (p ≤ 0.01) and increase in pSTAT1 activation (p ≤ 0.001). No significant increase of any analyzed signaling step was observed in the radioresistant cell lines. This differentially activated intracellular immune signaling was also transferred to extracellular immune alterations. The radiosensitive cell lines showed an increase in immunogenic cell surface ligands like PD-L1 and CD137L, while the radioresistant cell lines showed less changes after IR. Further, different changes in the secreted chemo- and cytokines were observed between the cell lines after IR. To test if external stimulation of the JAK/STAT cascade could lead to radiosensitization in the resistant cell lines, cells were treated with IFNß1. Monotreatment in an acute setting by 2h IFNß1 treatment and 46h recovery lead to a significantly decreased cellular survival only in the radiosensitive cell lines (p ≤ 0.001). Chronic IFNß1 treatment for continuous 48h was less effective in reducing the cellular survival (p ≤ 0.05). Combined treatment of IFNß1 with 4 Gy IR lead to a small radiosensitization in both, the radioresistant and the radiosensitive cell lines. Additionally, the replication speed was significantly enhanced due to IFNß1 treatment in the radiosensitive cell lines (p ≤ 0.01) and differences in foci formation could be observed. Based on these results, the increase of DNA damage and replication stress by inhibition of e.g. PARP1, ATR or CHK1 seems to be a promising approach and is currently being investigated in our model system.

Conclusion:

Our results strongly indicate a connection between radioresistance and the reduced activation of the intracellular immune signaling pathway cGAS/STING, associated with an altered expression of cell surface immune regulatory molecules. The observation, that stimulation of this pathway may increase radiosensitivity might offer new therapeutic opportunities.

Keywords: Radioresistance, BRCA1, cGAS/STING

2194

Digital Poster

Immune cell subpopulation changes after different therapeutic modalities of TNBC complex therapy

Zsuzsa S Kocsis 1 , Gyöngyvér Orsolya Sándor 1 , Gyöngyi Farkas 1 , Gábor Székely 1 , Gábor Rubovszky 2 , Borbála Székely 2 , Ákos Sávolt 3 , Viktor Smanykó 4 , Zoltán Takácsi-Nagy 4,5 , Csaba Polgár 4,5 , Zsolt Jurányi 1 1 National Institute of Oncology, Department of Radiobiology and Diagnostic Onco-Cytogenetics and the National Tumor Biology Laboratory, Centre of Radiotherapy, Budapest, Hungary. 2 National Institute of Oncology, Department of Clinical Pharmacology, Chest and Abdominal Tumours Chemotherapy "B", Budapest, Hungary. 3 National Institute of Oncology, Department of Breast and Sarcoma Surgery, Budapest, Hungary. 4 National Institute of Oncology, Centre of Radiotherapy and the National Tumor Biology Laboratory, Budapest, Hungary. 5 Semmelweis University, Department of Oncology, Faculty of Medicine, Budapest, Hungary

Purpose/Objective:

The advance of immunotherapy is possibly limited by the previous or parallel treatment modalities (for example radiotherapy) killing the targeted immune cells. However, it is already described, that not all immune cell populations are depleted as a result of radiation or chemotherapy. We measured NK and cytotoxic T cell