Investigation of mechanism of abscopal effect and therapeutic application

• Project/Area Number: 15K06870
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Teikyo University (2016-2018); The University of Tokyo (2015)
• Principal Investigator: Shiraishi Kenshiro 帝京大学, 医学部, 教授 (40447404)
• Co-Investigator(Kenkyū-buntansha): 中川 恵一 東京大学, 医学部附属病院, 准教授 (80188896)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: アブスコパル / 腫瘍免疫 / 放射線治療

Outline of Final Research Achievements

We found that innate immunity plays a critical role for induction of abscopal effect triggered by local irradiation based on our basic research using tumor-bearing mice. Possible effector cells include CD4/CD8-positive T cells and antigen prisenting cells. Significant difference of the effect was not seen in fractionation schedule (conventional fx vs hypofx).
Although research duration was extended, we also found putative minimum unit for induction of abscopal effect with chemically-composed partial peptides of ECI301, which run through HMGB1 and HSP70. Further study development is warranted on the gene level to elucidate and understand this effect.

Academic Significance and Societal Importance of the Research Achievements

手術や放射線治療の高精度化に依存する局所制御能の向上と同時に、進行再発例に対しても有効かつ低侵襲の治療法を研究・開発することは重要なテーマである。医学物理の技術革新のみに頼らず、生体に備わる免疫応答を増幅し全身的な治療効果すなわちアブスコパル効果を惹起させることは腫瘍学上大変斬新で魅力的であり、革新的な次世代の治療法に貢献し得る。
とりわけ近年の免疫チェックポイント阻害剤開発によるがん診療の劇的な変革にあたり、放射線治療の適切な併用によりアブスコパル効果を誘導、免疫学的機序に基づくそのメカニズムを細胞分子レベルで詳細に解析することは次世代の腫瘍治療戦略が構築でき大きく社会貢献を果たすものである。

Research Products

• [Journal Article] Results of a nationwide survey on Japanese clinical practice in breast-conserving radiotherapy for breast cancer. (2019)
  • Author(s): Aibe N, Karasawa K, Aoki M,Akahane K, Ogawa Y, Ogo E, Kanamori S, Kawamori J, Saito A, Shiraishi K, Sekine H, Tachiiri S, Yoshimura M, Yamauchi C.
  • Journal Title: Journal of Radiation Research Volume: 60 Issue: 1 Pages: 142-149
  • DOI: 10.1093/jrr/rry095
  • NAID: 120006645318
  • Peer Reviewed / Open Access
• [Journal Article] Robot-assisted radical prostatectomy versus volumetric modulated arc therapy: comparison of front-line therapies for localized prostate cancer (2019)
  • Author(s): Taguchi S, Shiraishi K, Fujimura T, Naito A, Kawai T, Nakagawa K, Abe O, Kume H, Fukuhara H
  • Journal Title: Radiotherapy and Oncology Volume: in press
  • Peer Reviewed
• [Journal Article] A primary analysis of a multicenter, prospective, single-arm, confirmatory trial of hypofractionated whole breast irradiation after breast-conserving surgery in Japan: JCOG0906. (2019)
  • Author(s): Nozaki M, Kagami Y, Shibata T, Nakamura K, Ito Y, Nishimura Y, Kawaguchi Y, Saito Y, Nagata Y, Matsumoto Y, Akimoto T, Hiraoka M; Radiation Therapy Study Group, Japan Clinical Oncology Group.
  • Journal Title: Jpn J Clin Oncol Volume: 49 Issue: 1 Pages: 57-62
  • DOI: 10.1093/jjco/hyy160
  • Peer Reviewed
• [Journal Article] Identification of the active portion of the CCL3 derivative reported to induce antitumor abscopal effect (2018)
  • Author(s): Tsuchiya Tomoko、Shiraishi Kenshiro、Nakagawa Keiichi、Kim Jae-Ryong、Kanegasaki Shiro
  • Journal Title: Clinical and Translational Radiation Oncology Volume: 10 Pages: 7-12
  • DOI: 10.1016/j.ctro.2018.02.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Denoising Projection Data with a Robust Adaptive Bilateral Filter in Low-Count SPECT (2018)
  • Author(s): Nakabayashi Susumu、Chikamatsu Takashi、Okamoto Takao、Kaminaga Tatsuro、Arai Norikazu、Kumagai Shinobu、Shiraishi Kenshiro、Okamoto Takahide、Kobayashi Takenori、Kotoku Jun’ichi
  • Journal Title: International Journal of Medical Physics, Clinical Engineering and Radiation Oncology Volume: 07 Issue: 03 Pages: 363-375
  • DOI: 10.4236/ijmpcero.2018.73030
  • Peer Reviewed / Open Access
• [Journal Article] Image quality improvement in cone-beam CT using the super-resolution technique (2018)
  • Author(s): Oyama Asuka、Kumagai Shinobu、Arai Norikazu、Takata Takeshi、Saikawa Yusuke、Shiraishi Kenshiro、Kobayashi Takenori、Kotoku Jun’ichi
  • Journal Title: Journal of Radiation Research Volume: in press Issue: 4 Pages: 501-510
  • DOI: 10.1093/jrr/rry019
  • Peer Reviewed / Open Access
• [Journal Article] Fast skin dose estimation system for interventional radiology (2017)
  • Author(s): Takata Takeshi、Kotoku Jun’ichi、Maejima Hideyuki、Kumagai Shinobu、Arai Norikazu、Kobayashi Takenori、Shiraishi Kenshiro、Yamamoto Masayoshi、Kondo Hiroshi、Furui Shigeru
  • Journal Title: Journal of Radiation Research Volume: 59 Issue: 2 Pages: 233-239
  • DOI: 10.1093/jrr/rrx062
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of a commercial automatic treatment planning system for prostate cancers. (2017)
  • Author(s): Nawa K, Haga A, Nomoto A, Sarmiento R, Norton I, Shiraishi K, Yamashita H, Nakagawa K.
  • Journal Title: Medical Dosimetry Volume: 42 Issue: 3 Pages: 203-209
  • DOI: 10.1016/j.meddos.2017.03.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Evaluation of a commercial automatic treatment planning system for prostate cancer (2017)
  • Author(s): Nawa K, Haga A, Nomoto A, Sarmiento R, Norton I, Shiraishi K, Yamashita H, Nakagawa K.
  • Journal Title: Medical Dosimetry Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Radiation-induced low-grade fibromyxoid sarcoma of the chest wall nine years subsequent to radiotherapy for breast carcinoma: A case report (2016)
  • Author(s): Shibata S, Shiraishi K, Yamashita H, Kobayashi R, Nakagawa K
  • Journal Title: Oncology Letters Volume: 11 Issue: 4 Pages: 2520-2524
  • DOI: 10.3892/ol.2016.4221
  • Peer Reviewed / Open Access
• [Journal Article] Impact of Gleason pattern 5 including tertiary pattern 5 on outcomes of salvage treatment for biochemical recurrence in pT2-3N0M0 prostate cancer (2016)
  • Author(s): Taguchi S, Shiraishi K, Fukuhara H, Nakagawa K, Morikawa T, Kakutani S, Takeshima Y, Miyazaki H, Fujimura T, Nakagawa T, Kume H, Homma Y.
  • Journal Title: International Journal of Clinical Oncology Volume: 21 Issue: 5 Pages: 975-980
  • DOI: 10.1007/s10147-016-0978-9
  • Peer Reviewed
• [Journal Article] Optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy: is ultra-early salvage radiotherapy beneficial? (2016)
  • Author(s): Taguchi S, Shiraishi K, Fukuhara H, Nakagawa K, Morikawa T, Naito A, Kakutani S, Takeshima Y, Miyazaki H, Nakagawa T, Fujimura T, Kume H, Homma Y.
  • Journal Title: Radiation Oncology Volume: 11 Issue: 1 Pages: 102-102
  • DOI: 10.1186/s13014-016-0671-1
  • Peer Reviewed / Open Access
• [Journal Article] Improvement in quality of life by using duloxetine for chemotherapy-induced peripheral neuropathy (CIPN): a case report. (2016)
  • Author(s): Okuma K, Shiraishi K, Kanai Y, Nakagawa K.
  • Journal Title: Support Care Cancer Volume: 24 Issue: 11 Pages: 4483-4485
  • DOI: 10.1007/s00520-016-3349-1
  • Peer Reviewed
• [Journal Article] Evaluation of In Vivo Volumetric Dosimetry for Prostate Cancer Using Electronic Portal Imaging Device (2016)
  • Author(s): 今江禄一，竹中重治，渡邉雄一，岡野由香里，根津 誠，三枝茂輝，竹内幸浩，矢野敬一, 芳賀昭弘, 白石憲史郎, 山下英臣, 中川恵一
  • Journal Title: Japanese Journal of Radiological Technology Volume: 72 Issue: 11 Pages: 1128-1136
  • DOI: 10.6009/jjrt.2016_JSRT_72.11.1128
  • NAID: 130005284228
  • ISSN: 0369-4305, 1881-4883
  • Peer Reviewed / Open Access
• [Journal Article] Omission of Axillary Lymph Node Dissection for Clinically Node Negative Early-Stage Breast Cancer Patients (2015)
  • Author(s): Kobayashi R, Shiraishi K, Iwase S, Ohtomo K, Nakagawa K.
  • Journal Title: Breast Cancer Volume: 22 Issue: 6 Pages: 657-663
  • DOI: 10.1007/s12282-014-0532-4
  • Peer Reviewed
• [Journal Article] Radical Prostatectomy versus External Beam Radiotherapy for cT1-4N0M0 Prostate Cancer: Comparison of Patient Outcomes Including Mortality (2015)
  • Author(s): Taguchi S, Fukuhara H*, Shiraishi K, Nakagawa K, Morikawa T, Kakutani S, Takeshima Y, Miyazaki H, Fujimura T, Nakagawa T, Kume H, Homma Y
  • Journal Title: PLoS One Volume: 10 Issue: 10 Pages: e0141123-e0141123
  • DOI: 10.1371/journal.pone.0141123
  • Peer Reviewed / Open Access
• [Journal Article] Stereotactic Body Radiotherapy Results for Pulmonary Oligometastases: A Two-Institution Collaborative Investigation (2015)
  • Author(s): Niibe Y, Yamashita H, Sekiguchi K, Takahashi W, Shiraishi K, Okuma K, Terahara A, Kawamori J, Nakagawa K
  • Journal Title: Anticancer Research Volume: 35 Pages: 4903-4908
  • Peer Reviewed
• [Presentation] Five year follow-up of prostate cancer patients treated with volumetric modulated arc therapy (VMAT). (2018)
  • Author(s): Ogita M, Yamamoto K, Shiraishi K, Sawayanagi S, Yamashita H, Nakagawa K.
  • Organizer: ESTRO (European Society for Therapeutic Radiology and Oncology Anniversary) 37
  • Int'l Joint Research
• [Presentation] A clinical trial on hypofractionated whole-breast irradiation after breast-conserving surgery. (2017)
  • Author(s): Nozaki M, Kagami Y, Shibata K, Nakamura Y, Ito Y, Nishimura Y, Kawaguchi Y, Saito Y, Nagata Y, Matsumoto Y, Akimoto T, Nishimura T, Uno T, Tsujino K, Kataoka M, Kodaira T, Shiraishi K, Inoue K, Isohashi F, Hiraoka M, Karasawa K, Izumi S, Sakurai H.
  • Organizer: ESTRO (European Society for Therapeutic Radiology and Oncology Anniversary) 36.
  • Int'l Joint Research
• [Presentation] Automatic chest X-ray screening with convolutional neural networks. (2017)
  • Author(s): Kotoku J, Hirose T, Kumagai S, Matsushima A, Shiraishi K, Arai N, Haga A, Kobayashi T.
  • Organizer: AAPM (American Association of Physicists in Medicine) 59th annual meeting & exhibition
  • Int'l Joint Research
• [Presentation] 乳房照射の照射方法について調査を踏まえた標準化に関する研究. (2017)
  • Author(s): 相部則博, 青木昌彦, 赤羽佳子, 小川恭弘, 淡河恵津世, 金森修一, 河守次郎, 齋藤アンネ優子, 白石憲史郎, 関根 広, 立入誠司, 山内智香子, 吉村通央, 唐澤久美子
  • Organizer: 日本放射線腫瘍学会第30回学術大会
• [Presentation] Visualize skin dose and air dose in virtual reality. (2017)
  • Author(s): Takata T, Kotoku J, Kobayashi T, Shiraishi K, Yamamoto M, Kondo H, Furui S.
  • Organizer: The 103nd Scientific Assembly and Annual Meeting of RSNA (Radiological Society of North America)
  • Int'l Joint Research
• [Presentation] 当院での前立腺癌IMRT治療成績と抗血栓薬服用有無での合併症の比較検討. (2017)
  • Author(s): 南谷優成, 鈴木めぐみ, 北口真由香, 新井範一, 熊谷 仁, 白石憲史郎
  • Organizer: 日本放射線腫瘍学会第30回学術大会
• [Presentation] CBCTを利用した前立腺癌IMRTにおける超音波膀胱容量測定装置の性能評価. (2017)
  • Author(s): 熊谷 仁, 上村亮平, 新井範一, 北口真由香, 南谷優成, 白石憲史郎
  • Organizer: 日本放射線腫瘍学会第30回学術大会
• [Presentation] 乳房温存療法における5mmマージン陽性基準下でのブースト照射の意義. (2016)
  • Author(s): 北口真由香, 白石憲史郎, 多田敬一郎, 河守次郎, 清水わか子, 福内 敦, 西 常博.
  • Organizer: 日本放射線腫瘍学会第29回学術大会
  • Place of Presentation: 国立京都国際会館（京都、京都）
  • Year and Date: 2016-11-25
• [Presentation] 前立腺全摘後の生化学的再発に対する救援放射線療法の最適なタイミングについて～超早期救済照射は有効か～ (2016)
  • Author(s): 田口 慧, 白石憲史郎, 福原 浩, 中川恵一, 森川鉄平, 中川 徹, 藤村哲也, 久米春樹, 本間之夫.
  • Organizer: 前立腺全摘後の生化学的再発に対する救援放射線療法の最適なタイミングについて～超早期救済照射は有効か～
  • Place of Presentation: パシフィコ横浜（神奈川、横浜）
  • Year and Date: 2016-10-22
• [Presentation] 乳房温存療法における5mmマージン陽性基準下でのブースト照射の意義. (2016)
  • Author(s): 白石憲史郎, 多田敬一郎, 河守次郎, 清水わか子, 福内 敦, 西 常博.
  • Organizer: 第54回日本癌治療学会学術集会, 神奈川, 2016.10.20-22
  • Place of Presentation: パシフィコ横浜（神奈川、横浜）
  • Year and Date: 2016-10-20
• [Presentation] 前立腺全摘後・生化学的再発の救済治療におけるGleasonパターン5の意義 (2016)
  • Author(s): 田口 慧, 福原 浩, 白石憲史郎, 中川恵一, 森川鉄平, 中川 徹, 藤村哲也, 久米春樹, 本間之夫.
  • Organizer: 第54回日本癌治療学会学術集会, 神奈川, 2016.10.20-22
  • Place of Presentation: パシフィコ横浜（神奈川、横浜）
  • Year and Date: 2016-10-20
• [Presentation] Impact of tumor bed boost on local control and survival after breast- conserving therapy under stringent ‘5 mm as positive margin’ criteria: Japanese experience. (2016)
  • Author(s): Shiraishi K, Tada K, Kawamori J, Ibukuro K, Fukuuchi A.
  • Organizer: Controversies in Breast Cancer (CoBrCa)
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2016-09-08
  • Int'l Joint Research
• [Presentation] Disease progression of metastatic breast cancer by first relapse site after definitive radiotherapy (2015)
  • Author(s): Shiraishi K, Nakagawa K, Kawamori J, Ibukuro K, Fukuuchi A, Nishi T, Shinozaki T
  • Organizer: The Breast Cancer Symposium
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2015-09-25
  • Int'l Joint Research
• [Presentation] ER陽性HER2陰性の乳房温存療法症例にKi-67 St Gallen 2013推奨閾値は影響するか (2015)
  • Author(s): 白石憲史郎, 小林伶子, 大熊加惠, 山本健太郎, 中川恵一
  • Organizer: 第23回日本乳癌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-02
• [Presentation] Impact of brachytherapy seeds on dose distributions for prostate VMAT: a phantom study (2015)
  • Author(s): Shiraishi K, Sakumi A, Haga A, Yamamoto K, Okuma K, Yoda K, Nakagawa K
  • Organizer: The 3rd ESTRO Forum
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2015-04-24
  • Int'l Joint Research
• [Presentation] 限局性前立腺癌に対するVMAT治療の5年成績 (2015)
  • Author(s): 白石憲史郎, 山本健太郎, 野元昭弘, 作美 明, 中川恵一
  • Organizer: 第74回日本医学放射線学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2015-04-16
• [Presentation] 研修医セミナー 前立腺癌の放射線治療 (2015)
  • Author(s): 白石憲史郎
  • Organizer: 第74回日本医学放射線学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2015-04-16
  • Invited