S2615
Radiobiology - Translational radiobiology
ESTRO 2026
Conclusion: Fractionation plays a key role in shaping RT-induced NK and CD8 ⁺ T cell responses, particularly through modulation of the NKG2A-Qa1 inhibitory pathway. Our findings support the rationale for combining normofractionated RT with dual P--L1/NKG2A blockade to enhance antitumor efficacy. Further studies are warranted to translate these results toward a phase II clinical trial. References: 1. Demaria S et al. Radiation dose and fraction in immunotherapy: one-size regimen does not fit all settings, so how does one choose? J Immunother Cancer. 2021, doi:10.1136/jitc-2020-0020382. Boustani J et al. The 6th R of Radiobiology: Reactivation of Anti- Tumor Immune Response. Cancers (Basel). 2019, doi:10.3390/cancers110608603. Baude J et al. Combining radiotherapy and NK cell-based therapies: The time has come. Int Rev Cell Mol Biol. 2023, doi:10.1016/bs.ircmb.2023.02.0034. Mirjolet C, et al. Novel platform for subcutaneous tumor irradiation in mice. Methods Cell Biol. 2023, doi:10.1016/bs.mcb.2023.06.004 Keywords: Fractionation, NK cells, Immunotherapy Digital Poster Highlight 1445 Cardiovascular genetic risk predicts survival in thoracic but not non-thoracic cancers Mohammad Akash 1 , Ahmed Salem 2 , Fatima Farhan 1 , Abdelrahman Mohammad Masheh 1 , Badie Abuzaid 1 , Lina Al-Zerikat 1 , Azadeh Abravan 3,4 1 Faculty of Medicine, The Hashemite University, Zarqa, Jordan. 2 Department of Anatomy, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan. 3 Institute of genetics and cancer, University of Edinburgh, Edinburgh, United Kingdom. 4 Division of cancer sciences, The University of Manchester, Manchester, United Kingdom Purpose/Objective: Cardiovascular disease (CVD) is a major competing cause of death in cancer patients, particularly in those receiving treatments associated with cardiac adverse- events. Although genome-wide polygenic risk scores for CVD1 have been validated in general populations, their prognostic relevance in oncology remains unclear. We developed a CVD-derived gene-expression score using genome-wide coronary artery disease (CAD) variant mapping and evaluated its prognostic association in thoracic and non-thoracic malignancies. Material/Methods: CAD-associated variants from a large GWAS1 (60,801 cases; 123,054 controls; 6.6 million SNPs) were mapped to coding genes using positional, eQTL, and chromatin-interaction pipelines in FUMA2, identifying
964 CVD-linked genes (Figure 1). Using TCGA RNA- sequencing data (n=4,458; 1,259 deaths), multivariable survival Cox regression (adjusted for age, sex, and stage) generated gene-specific prognostic coefficients. A weighted expression score (CVDz) was computed using standardised expression and Cox weights (CVDz = Σ (wi × zi) / Σ wi, wi = Cox coefficients, zi = standardised expression). Restricted cubic splines assessed dose–response relationships. Patients were stratified into a thoracic cohort (breast cancer, lung adenocarcinoma, lung squamous; n=2,096; 543 deaths), in whom cardiac-adjacent radiotherapy and/or anthracyclines are typically administered, and a non-thoracic control cohort without known cardiotoxic exposures (prostate, bladder, colorectal, cervical, glioblastoma; n=2,362; 716 deaths). External validation used anthracycline-treated breast cancer (GSE25066) and stage 1-2 lung adenocarcinoma (GSE31210) cohorts.
Made with FlippingBook - Share PDF online