S2508 vessel/platelet - derived growth factor receptor β + perivascular cell disintegration is involved in vascular injury and bone loss in radiation - induced bone damage [J]. Cell Proliferat, 2023, 56(7). Keywords: FLASH radiotherapy, bone development
Radiobiology - Biology of novel irradiation techniques
ESTRO 2026
radio-immunotherapy combinations. Keywords: minibeam radiation therapy, tumor microenvironment
Digital Poster Highlight 2052
FLASH Radiotherapy in pancreatic cancer: tumor growth and metastatic dissemination using the CAM Model Paola Puccini 1,2 , Alessandra Gonnelli 1,2 , Noemi Giannini 1,2 , Giovanni Gadducci 1,2 , Patrizia Sarogni 2 , Valentina Frusca 2 , Katsiaryna Kharkauskaya 1 , Cecilia Trippa 1 , Valerio Voliani 2,3 , Fabiola Paiar 1,4 1 Radiation Oncology Unit, Azienda Ospedaliero- Universitaria Pisana, Pisa, Italy. 2 Center for Nanotechnology Innovation@NEST, Istituto Italiano di Tecnologia, Pisa, Italy. 3 Department of Pharmacy, School of Medical and 508 Pharmaceutical Sciences, University of Genoa, Genova, Italy. 4 Centro Pisano Multidisciplinare Sulla Ricerca e Implementazione Clinica Della Flash Radiotherapy (CPFR@CISUP), University of Pisa, Pisa, Italy Purpose/Objective: To investigate the effects of FLASH radiotherapy (FLASH RT) on tumor growth and metastatic behavior of pancreatic adenocarcinoma cells using the chick chorioallantoic membrane (CAM) model, comparing FLASH RT with conventional dose-rate irradiation (CONV RT). Material/Methods: BxPC-3 human pancreatic cancer cells were grafted onto the CAM of fertilized chicken eggs. Tumors were irradiated with 2 Gy either with FLASH RT (240 Gy/s) or CONV RT (6 Gy/min) using Electron FLASH Linac on embryonic development day 10 (EDD10). Tumor growth was monitored daily until embryonic development day 17 (EDD17) via digital microscopy (DinoLite). Metastatic spread was assessed visually on the upper CAM and quantitatively in the lower CAM by qPCR of human Alu sequences. A complementary experiment with GFP-labeled cells enhanced visualization of tumor dissemination. Results: Both FLASH and CONV RT significantly reduced primary tumor growth compared with controls (p<0.05). Tumors in the CONV group appeared smaller and more compact, whereas FLASH-treated tumors maintained a slightly more vascularized appearance. Embryo survival was markedly higher after FLASH RT, suggesting reduced normal tissue toxicity consistent with the FLASH effect. Qualitative assessment revealed comparable patterns of metastatic dissemination in treated and control groups, while qPCR analysis confirmed no statistically significant differences in the number of metastatic events between FLASH, CONV,
Proffered Paper 1725
MBRT Combined with Bevacizumab Unlocks Antitumor Immunity via ICAM1/LFA1-Mediated CD8+ T Cell Infiltration Meihua Chen, Zengyi Fang, Jinyi Lang Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Chengdu, China Purpose/Objective: The dysfunctional tumor vasculature impedes CD8+ T cell infiltration, representing a major barrier to effective cancer immunotherapy. While Minibeam radiation therapy (MBRT) combined with bevacizumab promotes vascular normalization, the precise immunological mechanisms driving the enhanced antitumor response remain elusive. Material/Methods: Using murine tumor models, we investigated the effects of combined MBRT and bevacizumab on vascular parameters (pericyte coverage, perfusion, permeability) and endothelial Intercellular Adhesion Molecule 1 (ICAM1) expression. Tumor-infiltrating
CD8+ T cells and their Lymphocyte Function- Associated Antigen 1 (LFA1) expression were
quantified by flow cytometry. The necessity of CD8+ T cells was definitively tested via depletion experiments. Results: The combination therapy significantly normalized tumor vasculature, as demonstrated by a ~2-fold increase in pericyte coverage and a ~40% reduction in vascular permeability, both of which were correlated with elevated VE-cadherin expression. Importantly, we observed a substantial upregulation of ICAM1 on tumor endothelial cells, which facilitated approximately a 2-fold increase in the infiltration of CD8+ T cells (Control vs. MBRT+Bev: 20.4% vs. 42.3%). These infiltrating T cells also exhibited enhanced LFA1 expression. The complete abrogation of the therapeutic effect following CD8+ T cell depletion further highlights their crucial role in mediating the antitumor response. Conclusion: Our findings unveil a novel mechanism whereby MBRT and bevacizumab act together to remodel the tumor microenvironment: by normalizing the vasculature and amplifying the ICAM1-LFA1 axis, they synergistically overcome the physical barrier to CD8+ T cell entry. This work provides a compelling rationale for targeting this pathway to enhance the efficacy of
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