Carbon-ion beams induce production of an immune mediator protein,high mobility group box 1, at levels comparable with X-ray irradiation |
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Authors: | Yuya Yoshimoto Takahiro Oike Noriyuki Okonogi Yoshiyuki Suzuki Ken Ando Hiro Sato Shin-ei Noda Mayu Isono Kousaku Mimura Koji Kono Takashi Nakano |
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Affiliation: | 1.Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan;2.Department of Radiation Oncology, Fukushima Medical University, 1-Hikariga-oka, Fukushima City 960-1295, Japan;3.Gunma University Heavy Ion Medical Center, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan;4.Department of Surgery, National University of Singapore, Level 8, NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228, Singapore |
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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. |
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Keywords: | HMGB1 carbon-ion beams anti-tumor immunity damage-associated molecular pattern |
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