title: Kill and spread the word: stimulation of antitumor immune responses in the context of radiotherapy.
abstract: Besides the direct, targeted effects of ionizing irradiation (x-ray) on cancer cells, namely DNA damage and cell death induction, indirect, nontargeted ones exist, which are mediated in large part by the immune system. Immunogenic forms of tumor cell death induced by x-ray, including immune modulating danger signals like the heat shock protein 70, adenosine triphosphate, and high-mobility group box 1 protein are presented. Further, antitumor effects exerted by cells of the innate (natural killer cells) as well as adaptive immune system (T cells activated by dendritic cells) are outlined. Tumor cell death inhibiting molecules such as survivin are introduced as suitable target for molecularly tailored therapies in combination with x-ray. Finally, reasonable combinations of immune therapies with radiotherapy are discussed.
authors.affiliation: Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany.
authors.forename: Udo S
authors.initials: US
authors.lastname: Gaipl
authors.forename: Gabriele
authors.initials: G
authors.lastname: Multhoff
authors.forename: Heike
authors.initials: H
authors.lastname: Scheithauer
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lauber
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hehlgans
authors.forename: Benjamin
authors.initials: B
authors.lastname: Frey
authors.forename: Franz
authors.initials: F
authors.lastname: Rödel
mesh_terms: D000255:Adenosine Triphosphate / Q000276:immunology; D004249:DNA Damage / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D024243:HMGB1 Protein / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000528:radiation effects*; D007113:Immunity, Innate / Q000528:radiation effects*; D007694:Killer Cells, Natural / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000532:radiotherapy*; D011878:Radiotherapy; D013601:T-Lymphocytes / Q000276:immunology; D014965:X-Rays
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000255:Adenosine Triphosphate
keywords: abscopal effect; annexin A5; dendritic cell; heat shock protein 70; high-mobility group box protein 1; immunogenic tumor cell death; immunotherapy; radiotherapy; survivin; vaccination