title: Early gene expression analysis in 9L orthotopic tumor-bearing rats identifies immune modulation in molecular response to synchrotron microbeam radiation therapy.
abstract: Synchrotron Microbeam Radiation Therapy (MRT) relies on the spatial fractionation of the synchrotron photon beam into parallel micro-beams applying several hundred of grays in their paths. Several works have reported the therapeutic interest of the radiotherapy modality at preclinical level, but biological mechanisms responsible for the described efficacy are not fully understood to date. The aim of this study was to identify the early transcriptomic responses of normal brain and glioma tissue in rats after MRT irradiation (400Gy). The transcriptomic analysis of similarly irradiated normal brain and tumor tissues was performed 6 hours after irradiation of 9 L orthotopically tumor-bearing rats. Pangenomic analysis revealed 1012 overexpressed and 497 repressed genes in the irradiated contralateral normal tissue and 344 induced and 210 repressed genes in tumor tissue. These genes were grouped in a total of 135 canonical pathways. More than half were common to both tissues with a predominance for immunity or inflammation (64 and 67% of genes for normal and tumor tissues, respectively). Several pathways involving HMGB1, toll-like receptors, C-type lectins and CD36 may serve as a link between biochemical changes triggered by irradiation and inflammation and immunological challenge. Most immune cell populations were involved: macrophages, dendritic cells, natural killer, T and B lymphocytes. Among them, our results highlighted the involvement of Th17 cell population, recently described in tumor. The immune response was regulated by a large network of mediators comprising growth factors, cytokines, lymphokines. In conclusion, early response to MRT is mainly based on inflammation and immunity which appear therefore as major contributors to MRT efficacy.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) - Unit 836, Team Nanomedecine and brain, La Tronche, France ; European Synchrotron Radiation Facility (ESRF), Biomedical Beamline, Grenoble, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Bouchet
authors.affiliation: Unité Mixte de Recherche 1090, Team Technlogical Advances for Genomics and Clinics (TAGC), Institut National de la Santé et de la Recherche Médicale (INSERM), Marseille, France ; Aix-Marseille Université, Marseille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sakakini
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) - Unit 836, Team Nanomedecine and brain, La Tronche, France ; Grenoble University Hospital, Grenoble, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: El Atifi
authors.affiliation: European Synchrotron Radiation Facility (ESRF), Biomedical Beamline, Grenoble, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Le Clec'h
authors.affiliation: European Synchrotron Radiation Facility (ESRF), Biomedical Beamline, Grenoble, France.
authors.forename: Elke
authors.initials: E
authors.lastname: Brauer
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) - Unit 836, Team Functional NeuroImaging and Brain Perfusion, La Tronche, France.
authors.forename: Anaïck
authors.initials: A
authors.lastname: Moisan
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) - Unit 836, Team Synchrotron Radiation and Medical Research, La Tronche, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Deman
authors.affiliation: Unité Mixte de Recherche 1090, Team Technlogical Advances for Genomics and Clinics (TAGC), Institut National de la Santé et de la Recherche Médicale (INSERM), Marseille, France ; Aix-Marseille Université, Marseille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Rihet
authors.affiliation: European Synchrotron Radiation Facility (ESRF), Biomedical Beamline, Grenoble, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Le Duc
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) - Unit 836, Team Nanomedecine and brain, La Tronche, France ; Grenoble University Hospital, Grenoble, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pelletier
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics / Q000528:radiation effects; D000818:Animals; D001921:Brain / Q000276:immunology / Q000528:radiation effects; D001932:Brain Neoplasms / Q000235:genetics* / Q000276:immunology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000528:radiation effects; D020869:Gene Expression Profiling; D005802:Genes, MHC Class II / Q000528:radiation effects*; D005910:Glioma / Q000235:genetics* / Q000276:immunology / Q000532:radiotherapy*; D007113:Immunity, Innate / Q000235:genetics / Q000528:radiation effects; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011878:Radiotherapy / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000276:immunology / Q000528:radiation effects; D017356:Synchrotrons