title: Investigation of Abscopal and Bystander Effects in Immunocompromised Mice After Exposure to Pencilbeam and Microbeam Synchrotron Radiation.
abstract: Out-of-field effects are of considerable interest in radiotherapy. The mechanisms are poorly understood but are thought to involve signaling processes, which induce responses in non-targeted cells and tissues. The immune response is thought to play a role. The goal of this research was to study the induction of abscopal effects in the bladders of NU-Foxn1 mice after irradiating their brains using Pencil Beam (PB) or microbeam (MRT) irradiation at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Athymic nude mice injected with F98 glioma cells into their right cerebral hemisphere 7 d earlier were treated with either MRT or PB. After recovery times of 2, 12, and 48 h, the urinary bladders were extracted and cultured as tissue explants for 24 h. The growth medium containing the potential signaling factors was harvested, filtered, and transferred to HaCaT reporter cells to assess their clonogenic survival and calcium signaling potential. The results show that in the tumor-free mice, both treatment modalities produce strong bystander/abscopal signals using the clonogenic reporter assay; however, the calcium data do not support a calcium channel mediated mechanism. The presence of a tumor reduces or reverses the effect. PB produced significantly stronger effects in the bladders of tumor-bearing animals. The authors conclude that immunocompromised mice produce signals, which can alter the response of unirradiated reporter cells; however, a novel mechanism appears to be involved.
authors.affiliation: *Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, L8S 4K1, Canada; †Department of Radiotherapy, Rostock University Medical Center, Südring 75, 18059 Rostock, Germany; ‡European Synchrotron Radiation Facility, BP 220 6, rue Jules Horowitz, 38043 Grenoble, France, §University of Bern, Hochschulstrasse 4, CH-3012 Bern, Switzerland; ** Niederwiesstrasse 13C, Untersiggenthal, Switzerland.
authors.forename: Cristian
authors.initials: C
authors.lastname: Fernandez-Palomo
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schültke
authors.forename: Elke
authors.initials: E
authors.lastname: Bräuer-Krisch
authors.forename: Jean Albert
authors.initials: JA
authors.lastname: Laissue
authors.forename: Hans
authors.initials: H
authors.lastname: Blattmann
authors.forename: Colin
authors.initials: C
authors.lastname: Seymour
authors.forename: Carmel
authors.initials: C
authors.lastname: Mothersill
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D024201:Bystander Effect / Q000276:immunology* / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000276:immunology / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D016867:Immunocompromised Host / Q000276:immunology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D061766:Proton Therapy; D011829:Radiation Dosage; D000069473:Radiation Dose Hypofractionation; D017356:Synchrotrons; D001743:Urinary Bladder / Q000276:immunology* / Q000473:pathology / Q000528:radiation effects*