title: Carbon-ion beams induce production of an immune mediator protein, high mobility group box 1, at levels comparable with X-ray irradiation.
abstract: X-ray radiotherapy activates tumor antigen-specific T-cell responses, and increases in the serum levels of high mobility group box 1 (HMGB1) induced by X-ray irradiation play a pivotal role in activating anti-tumor immunity. Here, we examined whether carbon-ion beams, as well as X-rays, can induce HMGB1 release from human cancer cell lines. The study examined five human cancer cell lines: TE2, KYSE70, A549, NCI-H460 and WiDr. The proportion of cells surviving X- or carbon-ion beam irradiation was assessed in a clonogenic assay. The D10, the dose at which 10% of cells survive, was calculated using a linear-quadratic model. HMGB1 levels in the culture supernatants were assessed by an ELISA. The D10 dose for X-rays in TE2, KYSE70, A549, NCI-H460 and WiDr cells was 2.1, 6.7, 8.0, 4.8 and 7.1 Gy, respectively, whereas that for carbon-ion beams was 0.9, 2.5, 2.7, 1.8 and 3.5 Gy, respectively. X-rays and carbon-ion beams significantly increased HMGB1 levels in the culture supernatants of A549, NCI-H460 and WiDr cells at 72 h post-irradiation with a D10 dose. Furthermore, irradiation with X-rays or carbon-ion beams significantly increased HMGB1 levels in the culture supernatants of all five cell lines at 96 h post-irradiation. There was no significant difference in the amount of HMGB1 induced by X-rays and carbon-ion beams at any time-point (except at 96 h for NCI-H460 cells); thus we conclude that comparable levels of HMGB1 were detected after irradiation with iso-survival doses of X-rays and carbon-ion beams.
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yoshimoto
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Oike
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Okonogi
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan Department of Radiation Oncology, Fukushima Medical University, 1-Hikariga-oka, Fukushima City 960-1295, Japan ysuzu@fmu.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Hiro
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Shin-ei
authors.initials: SE
authors.lastname: Noda
authors.affiliation: Gunma University Heavy Ion Medical Center, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Isono
authors.affiliation: Department of Surgery, National University of Singapore, Level 8, NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228, Singapore.
authors.forename: Kousaku
authors.initials: K
authors.lastname: Mimura
authors.affiliation: Department of Surgery, National University of Singapore, Level 8, NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228, Singapore.
authors.forename: Koji
authors.initials: K
authors.lastname: Kono
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D002244:Carbon; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D024243:HMGB1 Protein / Q000378:metabolism*; D020450:Heavy Ions; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism; D007928:Lethal Dose 50; D009374:Neoplasms, Experimental / Q000378:metabolism*; D011829:Radiation Dosage; D014965:X-Rays
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D007155:Immunologic Factors; D002244:Carbon
keywords: HMGB1; anti-tumor immunity; carbon-ion beams; damage-associated molecular pattern