title: Antitumor immunity induced after α irradiation.
abstract: Radioimmunotherapy (RIT) is a therapeutic modality that allows delivering of ionizing radiation directly to targeted cancer cells. Conventional RIT uses β-emitting radioisotopes, but recently, a growing interest has emerged for the clinical development of α particles. α emitters are ideal for killing isolated or small clusters of tumor cells, thanks to their specific characteristics (high linear energy transfer and short path in the tissue), and their effect is less dependent on dose rate, tissue oxygenation, or cell cycle status than γ and X rays. Several studies have been performed to describe α emitter radiobiology and cell death mechanisms induced after α irradiation. But so far, no investigation has been undertaken to analyze the impact of α particles on the immune system, when several studies have shown that external irradiation, using γ and X rays, can foster an antitumor immune response. Therefore, we decided to evaluate the immunogenicity of murine adenocarcinoma MC-38 after bismuth-213 ((213)Bi) irradiation using a vaccination approach. In vivo studies performed in immunocompetent C57Bl/6 mice induced a protective antitumor response that is mediated by tumor-specific T cells. The molecular mechanisms potentially involved in the activation of adaptative immunity were also investigated by in vitro studies. We observed that (213)Bi-treated MC-38 cells release "danger signals" and activate dendritic cells. Our results demonstrate that α irradiation can stimulate adaptive immunity, elicits an efficient antitumor protection, and therefore is an immunogenic cell death inducer, which provides an attractive complement to its direct cytolytic effect on tumor cells.
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; CNRS, Nantes, France; University of Nantes, Nantes, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Gorin
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; CNRS, Nantes, France; University of Nantes, Nantes, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Ménager
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; CNRS, Nantes, France; University of Nantes, Nantes, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gouard
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; CNRS, Nantes, France; University of Nantes, Nantes, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Maurel
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; CNRS, Nantes, France; University of Nantes, Nantes, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Guilloux
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; CNRS, Nantes, France; University of Nantes, Nantes, France; Nuclear Medicine Department, CHU Nantes, Nantes, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Faivre-Chauvet
authors.affiliation: Institute for Transuranium Elements, Karlsruhe, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Morgenstern
authors.affiliation: Institute for Transuranium Elements, Karlsruhe, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Bruchertseifer
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; CNRS, Nantes, France; University of Nantes, Nantes, France; Institut de Cancérologie de l'Ouest, Saint-Herblain, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Chérel
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; CNRS, Nantes, France; University of Nantes, Nantes, France.
authors.forename: François
authors.initials: F
authors.lastname: Davodeau
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; CNRS, Nantes, France; University of Nantes, Nantes, France. Electronic address: Joelle.Gaschet@univ-nantes.fr.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Gaschet
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D056747:Immunomodulation / Q000528:radiation effects*; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology; D047368:Tumor Burden / Q000276:immunology
chemical_list: D019496:Cancer Vaccines