Abstract 5000: Low dose ionizing radiation elicits the extrusion of neutrophil extracellular traps

Abstract

Abstract The majority of cancer patients undergo radiotherapy interventions at some point in their clinical management with unintended irradiation of blood vessels. We show that very low γ-irradiation doses (0.5-1 Gy) of human and mouse neutrophils elicit neutrophil extracellular trap (NET) formation in a manner dependent on oxidative stress, NADPH oxidase activity and autocrine interleukin-8. Radiation-induced NETs interfere with NK- and T-cell cytotoxicity-repelling effector lymphocytes away from tumor cells. As a consequence, pre-injection of irradiation-induced NETs increases the number of successful metastases in mouse tumor models. Increases in circulating NETs are readily detected in series of patients following radiotherapy interventions. Our results reveal new mechanisms whose knowledge may help to improve the efficacy and safety of radiotherapy, especially when used in combination with immunotherapy approaches. Citation Format: Alvaro Teijeira, Ana Martinez-Riaño, Beatrice Pinci, Almudena Manzanal, Paula Molero, Maria E. Rodriguez- Ruiz, Ignacio Melero. Low dose ionizing radiation elicits the extrusion of neutrophil extracellular traps [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5000.