Basic and clinical research about radiation-induced anti-tumor immunity

• Project/Area Number: 24591833
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Fukushima Medical University (2014); Gunma University (2012-2013)
• Principal Investigator: SUZUKI YOSHIYUKI 福島県立医科大学, 医学部, 教授 (60334116)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 放射線治療 / 腫瘍免疫 / HLA / HMGB1 / 免疫療法 / 放射線 / Ｘ線 / 炭素イオン線 / 抗腫瘍免疫 / HLA class I / MHC Class I / 細胞障害性Tリンパ球 / MHC

Outline of Final Research Achievements

I investigated about radiation-induced anti-tumor immunity in vitro and in vivo and reported about 1) The tumor antigen–specific T-cell response was induced by chemoradiotherapy in patients with esophageal squamous cell cancer, 2) Stress protein, HMGB1, released after irradiation played important role in the activation of tumor specific anti-tumor immunity, 3) In patients with rectal cancer, hyperthermo-chemo-radiotherapy enhaced the expression of HLA class-I in the tumor cells, and 4) In a mouse model, the immune response plays an important role in local and systemic therapeutic efficacies of radiotherapy, which can be augmented by immune checkpoint blockade (antiCTLA4 antibody etc.).

Research Products

• [Journal Article] Carbon-ion beams induce production of an immune mediator protein, high mobility group box 1, at levels comparable with X-ray irradiation. (2015)
  • Author(s): Yoshimoto Y, Oike T, Okonogi N, Suzuki Y, Ando K, Sato H, Noda SE, Isono M, Mimura K, Kono K, Nakano T.
  • Journal Title: J Radiat Res Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] HLA class I expression and its alteration by preoperative hyperthermo-chemoradiotherapy in patients with rectal cancer. (2014)
  • Author(s): Sato H, Suzuki Y, Ide M, Katoh T, Noda SE, Ando K, Oike T, Yoshimoto Y, Okonogi N, Mimura K, Asao T, Kuwano H, Nakano T.
  • Journal Title: PLoS One. Volume: 9(9) Issue: 9 Pages: e108122-e108122
  • DOI: 10.1371/journal.pone.0108122
  • Peer Reviewed / Open Access
• [Journal Article] Therapeutic potential of highly cytotoxic natural killer cells for gastric cancer. (2014)
  • Author(s): Mimura K, Kamiya T, Shiraishi K, Kua LF, Shabbir A, So J, Yong WP, Suzuki Y, Yoshimoto Y, Nakano T, Fujii H, Campana D, Kono K.
  • Journal Title: Int J Cancer. Volume: 135(6) Issue: 6 Pages: 1390-8
  • DOI: 10.1002/ijc.28780
  • Peer Reviewed
• [Journal Article] Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by ctla-4 blockade in a mouse model. (2014)
  • Author(s): Yoshimoto Y, Suzuki Y, Mimura K, Ando K, Oike T, Sato H, Okonogi N, Maruyama T, Izawa S, Noda SE, Fujii H, Kono K, Nakano T.
  • Journal Title: PLoS One. Volume: 9(3) Issue: 3 Pages: e92572-e92572
  • DOI: 10.1371/journal.pone.0092572
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of mitogen-activated protein kinase pathway can induce upregulation of human leukocyte antigen class I without PD-L1-upregulation in contrast to interferon-γ treatment. (2014)
  • Author(s): Mimura K, Kua LF, Shiraishi K, Kee Siang L, Shabbir A, Komachi M, Suzuki Y, Nakano T, Yong WP, So J, Kono K.
  • Journal Title: Cancer Sci. Volume: 105(10) Issue: 10 Pages: 1236-44
  • DOI: 10.1111/cas.12503
  • Peer Reviewed
• [Journal Article] Changes in bone mineral density in uterine cervical cancer patients after radiation therapy. (2013)
  • Author(s): Okonogi N, Saitoh J, Suzuki Y, Noda SE, Ohno T, Oike T, Ohkubo Y, Ando K, Sato H, Nakano T.
  • Journal Title: Int J Radiat Oncol Biol Phys. Volume: 87(5) Issue: 5 Pages: 968-74
  • DOI: 10.1016/j.ijrobp.2013.08.036
  • Peer Reviewed
• [Journal Article] Radiotherapy plus concomitant adjuvant temozolomide for glioblastoma: Japanese mono-institutional results. (2013)
  • Author(s): Oike T, Suzuki Y, Sugawara K, Shirai K, Noda SE, Tamaki T, Nagaishi M, Yokoo H, Nakazato Y, Nakano T.
  • Journal Title: PLoS One. Volume: 8(11): Issue: 11 Pages: e78943-e78943
  • DOI: 10.1371/journal.pone.0078943
  • Peer Reviewed
• [Journal Article] Five-fraction CyberKnife radiotherapy for large brain metastases in critical areas: impact on the surrounding brain volumes circumscribed with a single dose equivalent of 14 Gy (V14) to avoid radiation necrosis. (2013)
  • Author(s): Inoue HK, Sato H, Seto K, Torikai K, Suzuki Y, Saitoh J, Noda SE, Nakano T.
  • Journal Title: J Radiat Res. Volume: 55(2) Issue: 2 Pages: 334-42
  • DOI: 10.1093/jrr/rrt127
  • Peer Reviewed
• [Journal Article] X irradiation changes dendritic spine morphology and density through reduction of cytoskeletal proteins in mature neurons. (2013)
  • Author(s): Shirai K, Mizui T, Suzuki Y, Okamoto M, Hanamura K, Yoshida Y, Hino M, Noda SE, Al-jahdari WS, Chakravarti A, Shirao T, Nakano T.
  • Journal Title: Radiat Res. Volume: 179(6) Issue: 5 Pages: 630-6
  • DOI: 10.1111/jog.12024
  • Peer Reviewed
• [Journal Article] Three-dimensional and Multienergy Gamma-ray Simultaneous Imaging by Using a Si/CdTe Compton Camera. (2013)
  • Author(s): Suzuki Y
  • Journal Title: Radiology Volume: 267(3) Issue: 3 Pages: 941-947
  • DOI: 10.1148/radiol.13121194
  • Peer Reviewed
• [Journal Article] Three-fraction Cyberknife radiotherapy for brain metastases in critical areas: referring to the risk evaluating radiation necrosis and the surrounding brain volumes circumscribed with a single dose equivalence of 14Gy (V14) (2013)
  • Author(s): Hiroshi K. INOUE
  • Journal Title: Journal of Radiation Research Volume: 54(3) Issue: 4 Pages: 1-9
  • DOI: 10.1093/jrr/rrt006
  • Peer Reviewed
• [Journal Article] Usefulness of double dose contrast-enhanced magnetic resonance imaging for clear delineation of gross tumor volume in stereotactic radiotherapy treatment planning of metastatic brain tumors (2013)
  • Author(s): Subedi KS, Takahashi T, Yamano T, Saitoh JI, Nishimura K, Suzuki Y, Ohno T, Nakano T.
  • Journal Title: J Radiat Res Volume: 54 Issue: 1 Pages: 135-139
  • DOI: 10.1093/jrr/rrs053
  • Peer Reviewed
• [Journal Article] Immunogenic tumor cell death induced by chemoradiotherapy in patients with esophageal squamous cell carcinoma (2012)
  • Author(s): Yoshiyuki Suzuki
  • Journal Title: Cancer Research Volume: 72 Issue: 16 Pages: 3967-3976
  • DOI: 10.1158/0008-5472.can-12-0851
  • Peer Reviewed
• [Journal Article] Pseudo-progression event during temozolomide combining chemoradiotherapy for malignant glioma (2012)
  • Author(s): Suzuki Y, Saleem W, Satoh Y, Wakatsuki M, Shirai K, Sugawara K, Noda SE, Okamoto M, Yoshimoto Y, Nakano T
  • Journal Title: Austral-Asian Journal of Cancer Volume: 11 Pages: 131-135
  • Peer Reviewed
• [Presentation] 放射線治療の高度化・個別化のためのトランスレーショナル・リサーチ (2014)
  • Author(s): 鈴木義行
  • Organizer: 日本放射線腫瘍学会第27回学術大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-12-11 – 2014-12-13
  • Invited
• [Presentation] 放射線により誘導される抗腫瘍免疫と治療効果に関する実験的検討 (2014)
  • Author(s): 鈴木 義行、吉本由哉 、三村耕作 、安藤謙 、尾池貴洋、丸山孝教、藤井秀樹、河野浩二、中野隆史
  • Organizer: 日本放射線腫瘍学会第27回学術大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-12-11 – 2014-12-13
• [Presentation] Carbon-ion beam and X-ray irradiation increase a release of an immune mediator protein high mobility group box 1 (HMGB1) in various human cancer cell lines (2014)
  • Author(s): Yoshiyuki Suzuki, Yuya Yoshimoto, Takahiro Oike, Noriyuki Okonogi, Ken Ando, Hiro Sato, Shin-ei Noda, Mayu Isono, Kousaku Mimura, Koji Kono, Takashi Nakano
  • Organizer: The 56th ASTRO's Annual Meeting
  • Place of Presentation: Moscone Center, San Francisco
  • Year and Date: 2014-09-14 – 2014-09-17
• [Presentation] 神経膠芽腫に対するtemozolomideを用いた化学放射線治療の臨床成績と、次の一手 (2014)
  • Author(s): 鈴木義行, 野田真永, 田巻倫明, 尾池貴洋, 中野隆史
  • Organizer: 第43回 放射線による制癌シンポジウム
  • Place of Presentation: メルパルク京都
  • Year and Date: 2014-07-11
  • Invited
• [Presentation] 放射線治療と抗腫瘍免疫～基礎研究から臨床試験、そして先進医療へ～ (2014)
  • Author(s): 鈴木義行
  • Organizer: 第50回 群馬放射線腫瘍研究会
  • Place of Presentation: 高崎シティーギャラリー
  • Year and Date: 2014-04-19
  • Invited
• [Presentation] 放射線による抗腫瘍免疫誘導-免疫放射線療法の可能性 (2013)
  • Author(s): 鈴木義行
  • Organizer: 第51回日本癌治療学会学術集会
  • Place of Presentation: 京都
  • Invited
• [Presentation] 重粒子線の生物学 (2013)
  • Author(s): 鈴木義行
  • Organizer: 第49回日本医学放射線学会秋季臨床大会
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] 食道扁平上皮癌患者における、化学放射線療法による抗原特異的免疫反応誘導 (2013)
  • Author(s): ３． 鈴木義行、三村耕作、吉本由哉、藤井秀樹、河野浩二、中野隆史
  • Organizer: 第22回日本癌病態治療研究会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Heavy-ion beam therapy (2013)
  • Author(s): Suzuki Y
  • Organizer: The 3rd meeting of International Society for Radiation Neurobiology
  • Place of Presentation: Nago, JAPAN
  • Invited
• [Presentation] Acute Toxicity of Carbon-ion Radiotherapy for Localized Prostate Cancer (2012)
  • Author(s): Suzuki Y, Katoh H, Ishikawa H, Kaminuma T, Tamaki T, Shirai K, Matsui H,Ohno T, Ito K, Suzuki K, Nakano T,
  • Organizer: 22nd International Conference on the Application of Accelerators in Research and Industry
  • Place of Presentation: Fort Worth, TX, USA
  • Invited
• [Presentation] 重粒子線治療: 脳腫瘍・頭蓋底腫瘍に対する現状と今後の展望
  • Author(s): 鈴木義行
  • Organizer: 東京女子医科大学病院 ガンマナイフ治療 6000 症例記念講演会
  • Place of Presentation: 東京
  • Invited