S2531
Radiobiology – Immuno-radiobiology
ESTRO 2026
Consistently, the quadruple therapy increased the frequency and cytotoxic cytokine production of tumor- specific CD8 ⁺ TILs in the abscopal tumor (p<0.05). FF modulated glycolysis and fatty-acid oxidation (FAO) in CD8 ⁺ TILs; scRNA-seq highlighted Cpt1a, the rate- limiting FAO enzyme, as a key regulator mediating a glycolysis-to-FAO shift in CD8 ⁺ TILs of the abscopal tumor. In vitro, FF enhanced LDRT-associated tumor- cell death and induced a metabolic shift toward glycolysis in tumor cells. Pharmacologic CPT1a inhibition in vivo attenuated therapeutic efficacy. Conclusion: Adding FF to hRT/LDRT and α PD-1 markedly enhanced abscopal tumor control in a CD8 ⁺ T-cell–dependent manner, associated with greater T-cell infiltration, increased cytotoxic function, and FAO-oriented metabolic reprogramming of TILs. Inhibition of Cpt1a attenuated the abscopal effect, supporting FAO promotion in CD8 ⁺ TILs as a promising strategy to enhance systemic effects of combined radioimmunotherapy. FF-mediated radiosensitization of LDRT-treated tumor cells may further contribute to the robust abscopal responses. Keywords: Immune checkpoint inhibitors, radiobiology Differential Patterns of Lymphocyte Depletion during Radiotherapy in Central Nervous System and Head-and-Neck Tumours Sarah Salih Al-Hamami 1,2 , Thao-Nguyen Pham 3 , Krist ý na Olsson He ř manová 4 , Samuel Kurucz 4 , Samuel Valable 5 , Jana Prausová 6 , Vladimír Vondrá č ek 4 , Juliette Thariat 3 , Jiri Kube š 6 1 2nd Faculty of Medicine, Charles University, Prague, Czech Republic. 2 Medical Oncology, The Christie, Manchester, United Kingdom. 3 Université de Caen Normandie, Normandie Université, Caen, France. 4 Department of Medical Physics, Proton Therapy Centre, Prague, Czech Republic. 5 Université de Caen Normandie, CNRS, Normandie Université ISTCT UMR6030, GIP CYCERON, F-14000, Caen, France. 6 Department of Radiation Oncology, Proton Therapy Centre, Prague, Czech Republic Digital Poster 2464
administered concurrently with tumor rechallenge, whereas early JAKi treatment did not weaken long- term immune protection. We conclude that JAKi causes partial suppression of the interferon pathway, allowing residual interferon signaling to persist and possibly maintain immune function compared to the complete blockade by anti-IFNaR1. These results highlight the importance of treatment timing in combining JAKi with RIT. Further studies are warranted to elucidate the underlying mechanisms of improved RIT outcomes after JAK inhibition. Keywords: Immunotherapy, Janus-Kinase inhibition PPARα Agonism Enhances Systemic T-Cell– Mediated Tumor Control through Metabolic Rewiring in combined RT/anti–PD-1 therapy Meidan Wang Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany Purpose/Objective: Combining radiotherapy (RT) with anti–PD-1 ( α PD-1) can elicit CD8 ⁺ T-cell–mediated local and systemic (abscopal) tumor control, yet many patients do not respond. Fenofibrate (FF), a clinically approved PPAR α agonist for hypercholesterolemia/hypertriglyceridemia, has shown preclinical antitumor activity . We tested whether FF augments RT + α PD-1 to strengthen systemic immunity in abscopal models. Material/Methods: Mice bearing bilateral B16 melanoma or C51 colon carcinoma received hypofractionated RT to the primary tumor (8 Gy × 3; hRT) and low-dose RT to the Digital Poster Highlight 2250 contralateral tumor (3 Gy × 3; LDRT). α PD-1 was administered weekly; FF was given once daily on weekdays. Tumor growth and survival were monitored. Tumor-specific CD8 ⁺ T cells, cytokine production, and metabolic features were assessed by flow cytometry. Effects of FF on tumor cells ± irradiation were tested in vitro. Single-cell RNA sequencing (scRNA-seq) of tetramer ⁺ CD8 ⁺ tumor- infiltrating lymphocytes (TILs) and in vivo inhibition studies identified key metabolic regulators. Results: Across both models, the quadruple regimen (hRT + LDRT + α PD-1 + FF) significantly outperformed all triple combinations in controlling primary and abscopal tumors and improving survival (n ≥ 6/group; p<0.05). In the C51 model, the quadruple therapy cured all mice at both the hRT- and LDRT-treated sites and was the only regimen achieving complete eradication of the LDRT-treated abscopal tumor. CD8 ⁺ T-cell depletion abrogated benefit, indicating CD8 ⁺ T-cell dependence.
Purpose/Objective: Lymphopenia is a recognized consequence of
radiotherapy, which may impair anti-tumour immune response and adversly affect clinical outcomes (1). Factors such as tumour location, nodal irradiation, and treatment characteristics can influence the extent of lymphocyte depletion. This study investigates the dynamics of circulating lymphocytes throughout radiotherapy in patients with head-and-neck cancer (HNC), typically treated with lymph node irradiation
Made with FlippingBook - Share PDF online