S2534
Radiobiology – Immuno-radiobiology
ESTRO 2026
neutron capture therapy (BNCT) for the treatment of head and neck squamous cell carcinoma (HNSCC). In Finland, BNCT is carried out by an accelerator-based in-hospital neutron source nuBeam at the Helsinki University Hospital. We are exploring sensitization potential of BNCT to immunotherapy in HNSCC and its efficacy to combat challenging HNSCC cases. Material/Methods: First, we studied the boron biodistribution, cytotoxicity, and uptake of BPA-F in three different head and neck cancer cell lines UT-SCC-14, UT-SCC- 42B, and UT-SCC-28 with varying LAT1 expression levels. Boron uptake studies were performed in vitro with 5-, 30-, and 120-min time points. Boron uptake in vivo was studied by using orthotopic HNSCC mouse model Rj:ATHYM-Foxn1nu/nu mice with UT-SCC-14 cells as well as syngeneic mouse oral carcinoma MOC1 and MOC2 mouse models. Due to compromising boron levels in wild type MOC1/2 mice, LAT1- overexpressing MOC1 and MOC2 models were generated. Results: In boron uptake in vitro, at the 30-min time point uptake was twice as high in UT-SCC-14 as in UT-SCC- 28, correlating with their respective LAT1 protein expression. In vivo, BPA-F showed low cytotoxicity and 3:1 tumor-to-blood and tumor-to-normal tissue ratios in UT-SCC-14 orthotopic mouse model as expected. Furthermore, our gene and protein expression analyses indicated distinct expression of SLC7A5 and LAT1 in UT-SCC-14 mouse model as well as in HNSCC patient samples. On the other hand, MOC1 and MOC2 mouse models expressed lower levels of SLC7A5 and LAT1 than UT-SCC-14 cells, which was supported by biodistribution studies. Conclusion: To investigate the ability of BNCT to sensitize head and neck tumors to immunotherapy, we established three- dimensional patient-derived fragment cultures (PDTFs). PDTFs are exposed to irradiation with BNCT and PD-1 immune checkpoint inhibitors pembrolizumab and nivolumab. To assess the immune responses, RNA sequencing, multiplex immunohistochemical staining and cytokine marker analysis are performed on treated PDTFs. Investigation on immune profiles of our pre-clinical models predisposed to combination treatment will provide insight on biological changes induced by combination treatment, introduce potential immune response markers, and reveal potential reactivation of immune cells suggesting potential for combination treatment of BNCT and immunotherapy in a clinical setting. Keywords: boron neutron capture therapy, BNCT, HNSCC
multiplex immunofluorescence showed no significant differences in T-cell infiltration or subset distribution across RT regimens or anatomical sites. RNA-seq revealed upregulation of immune-related pathways with a balanced pattern of immunostimulatory (e.g., IFN- γ , TNF- α ) and immunosuppressive (e.g., STAT5, STAT3) signaling, alongside downregulation of cell- proliferation-related genes. Conclusion: Preoperative hypofractionated RT in MSS CRC induced an expansion of CD4 ⁺ TEMRA cells and increased T-cell clonality. Despite stable intratumoural T-cell density, transcriptomic analyses indicated activation of immune pathways. Further studies are needed to characterize these responses and identify targets for effective RT– immunotherapy combinations. The limited number of Low-RT, Out-RT, lung, and primary lesions prevents strong conclusions for these subgroups. References: 1. Llosa, N.J., et al. Cancer Discov, 2015. 5(1): p. 43-51.2. Le, D.T., et al. New England Journal of Medicine, 2015. 372(26): p. 2509- 2520.3. Demaria, S., et al. Int J Radiat Oncol Biol Phys, 2004. 58(3): p. 862-70.4. Segal, N.H., et al. Clin Cancer Res, 2021. 27(8): p. 2200-2208. Keywords: Colorectal cancer, Immunomodulatory radiotherapy Preclinical investigation of BNCT for the treatment of HNSCC and its potential for combination with immunotherapy Arina Värä 1 , Henna Pehkonen 1 , Surachet Imlimthan 2 , Piia-Riitta Karhemo 1 , Juulia Järvinen 3 , Jelena Matovic 2 , Anna Rintala 4 , Heikki Joensuu 4 , Mikko Tenhunen 4 , Liisa Porra 4 , Lauri Wendland 4 , Tanja Mälkiä 4 , Jarkko Rautio 3 , Filip Ekholm 2 , Antti Mäkitie 5,6 , Mirkka Sarparanta 2 , Outi Monni 1,6 1 Applied Tumor Genomics Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland. 2 Department of Chemistry, University of Helsinki, Helsinki, Finland. 3 School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Digital Poster 2847 Finland. 4 Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland. 5 Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. 6 iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Purpose/Objective: Our aim is to use different pre-clinical approaches for optimization of the therapeutic efficacy of boron
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