Elucidation of a mechanism of abscopal effect -Innovative cancer treatment strategy-

• Project/Area Number: 18H02696
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Teikyo University
• Principal Investigator: Shiraishi Kenshiro 帝京大学, 医学部, 教授 (40447404)
• Co-Investigator(Kenkyū-buntansha): 垣見 和宏 東京大学, 医学部附属病院, 特任教授 (80273358)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2019: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2018: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: アブスコパル / 腫瘍免疫 / 放射線治療

Outline of Final Research Achievements

Intentional enhancement of immune response of the host to induce a systemic abscopal effect is very attractive in oncology and represents an innovative next-generation therapeutic approach. The aim of this study was to establish the scientific basis for the development of a therapeutic strategy to expand the response of irradiation from local to systemic therapy using immune checkpoint inhibitors, focusing on tumor immunity, which has been attracting the greatest attention in recent years. Since the biomarker/specific neoantigen/optimal irradiation method was unknown, a prospective clinical study with SBRT was considered.
We thoroughly investigated the status of domestic and international research and established a cross-sectional cooperative system to administer PD-(L)1 antibody, though invasive procedures were delayed due to the impact of COVID-19 and other factors, which affected the execution of the study.

Academic Significance and Societal Importance of the Research Achievements

本研究は、癌治療の開発・研究における放射線腫瘍学と腫瘍免疫学２つの重点項目を融合させた斬新で独創的な研究である。経験的現象論に過ぎなかった"abscopal effect"を分子レベルで解明・誘導することは今後の癌治療体系を根源的に変貌させる可能性を有しており、精力的に取り組むべき課題だからである。進行再発癌患者に適切な線量の放射線を照射することで局所から全身治療へと発展させ、重篤な合併症もなく癌の進行を抑制する腫瘍治療学の新たなアプローチとなり得る。とりわけ臨床応用を意識した研究成果は、トランスレーショナル・リサーチ推進の原動力となり社会・国民的要求に応えるものである。

Research Products

• [Journal Article] Classification of chest X-ray images by incorporation of medical domain knowledge into operation branch networks (2023)
  • Author(s): Tsuji T, Hirata Y, Kusunose K, Sata M, Kumagai S, Shiraishi K, Kotoku J
  • Journal Title: BMC Medical Imaging Volume: 23 Issue: 1 Pages: 1-18
  • DOI: 10.1186/s12880-023-01019-0
  • Peer Reviewed / Open Access
• [Journal Article] Introduction of Medical Physics Course at Teikyo University (2022)
  • Author(s): Kotoku J, Kumagai S, Uehara R, Shiraishi K
  • Journal Title: Japanese Journal of Medical Physics (Igakubutsuri) Volume: 42 Issue: 2 Pages: 106-109
  • DOI: 10.11323/jjmp.42.2_106
  • ISSN: 1345-5354, 2186-9634
  • Year and Date: 2022-06-30
  • Open Access
• [Journal Article] Catalyst HDを利用したマーカーレス放射線治療 (2022)
  • Author(s): 白石憲史郎
  • Journal Title: 放射線治療BOOK2022（RadFan2022年11月臨時増刊号） Volume: 20 Pages: 30-35
• [Journal Article] A phase II study of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small-cell lung cancer in Japan (SAMURAI study): primary analysis (2022)
  • Author(s): Tanaka H, Tanzawa S, Shiraishi K, et al.
  • Journal Title: Ther Adv Med Oncol Volume: 14 Pages: 1-14
  • DOI: 10.1177/17588359221142786
  • Peer Reviewed / Open Access
• [Journal Article] Prospective analysis of factors precluding the initiation of durvalumab from an interim analysis of a phase II trial of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small cell lung cancer in Japan (SAMURAI study) (2022)
  • Author(s): Tanzawa S, Makiguchi T, Shiraishi K, et al.
  • Journal Title: Ther Adv Med Oncol Volume: 14 Pages: 1-14
  • DOI: 10.1177/17588359221116603
  • Peer Reviewed / Open Access
• [Journal Article] First experience of 192Ir source stuck event during high-dose-rate brachytherapy in Japan (2020)
  • Author(s): Kumagai Shinobu、Arai Norikazu、Takata Takeshi、Kon Daisuke、Saitoh Toshiya、Oba Hiroshi、Furui Shigeru、Kotoku Jun’ichi、Shiraishi Kenshiro
  • Journal Title: Journal of Contemporary Brachytherapy Volume: 12 Issue: 1 Pages: 53-60
  • DOI: 10.5114/jcb.2020.92401
  • Peer Reviewed / Open Access
• [Journal Article] Immersive radiation experience for interventional radiology with virtual reality radiation dose visualization and fast Monte Carlo dose estimation for the visualization. (2020)
  • Author(s): Takata T, Kondo H, Yamamoto M, Shiraishi K, Kobayashi T, Okamoto T, Oba H, Furui S, Kotoku J.
  • Journal Title: Interventional Radiology Volume: in press
  • Peer Reviewed
• [Journal Article] Classification of optical coherence tomography images using a capsule network (2020)
  • Author(s): Tsuji Takumasa、Hirose Yuta、Fujimori Kohei、Hirose Takuya、Oyama Asuka、Saikawa Yusuke、Mimura Tatsuya、Shiraishi Kenshiro、Kobayashi Takenori、Mizota Atsushi、Kotoku Jun’ichi
  • Journal Title: BMC Ophthalmology Volume: 20 Issue: 1 Pages: 114-114
  • DOI: 10.1186/s12886-020-01382-4
  • Peer Reviewed / Open Access
• [Journal Article] Clinical outcome of adjuvant radiotherapy for squamous cell carcinoma of the breast; a multicenter retrospective cohort study. (2020)
  • Author(s): Ogita M, Shiraishi K, Karasawa K, Tokumasu K, Nakajima N, Chang T, Kawamori J, Yamashita H, Nakagawa K
  • Journal Title: The Breast Volume: in press Pages: 88-94
  • DOI: 10.1016/j.breast.2020.05.003
  • Peer Reviewed
• [Journal Article] Classification of primary liver cancer with immunosuppression mechanisms and correlation with genomic alterations. (2020)
  • Author(s): Fujita M, Yamaguchi R, Hasegawa T, Shimada S, Arihiro K, Hayashi S, Maejima K, Nakano K, Fujimoto A, Ono A, Aikata H, Ueno M, Hayami S, Tanaka H, Miyano S, Yamaue H, Chayama K, Kakimi K, Tanaka S, Imoto S, Nakagawa H.
  • Journal Title: EBioMedicine Volume: 53 Pages: 102659-102659
  • DOI: 10.1016/j.ebiom.2020.102659
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hepatic tumor classification using texture and topology analysis of non-contrast-enhanced three-dimensional T1-weighted MR images with a radiomics approach (2019)
  • Author(s): Oyama Asuka、Hiraoka Yasuaki、Obayashi Ippei、Saikawa Yusuke、Furui Shigeru、Shiraishi Kenshiro、Kumagai Shinobu、Hayashi Tatsuya、Kotoku Jun’ichi
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 8764-8764
  • DOI: 10.1038/s41598-019-45283-z
  • 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: 140 Pages: 62-67
  • DOI: 10.1016/j.radonc.2019.05.015
  • Peer Reviewed
• [Journal Article] Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti?Programmed Cell Death-1 Therapy in NSCLC (2019)
  • Author(s): Ohue Yoshihiro、Kurose Koji、Karasaki Takahiro、Isobe Midori、Yamaoka Takaaki、Futami Junichiro、Irei Isao、Masuda Takeshi、Fukuda Masaaki、Kinoshita Akitoshi、Matsushita Hirokazu、Shimizu Katsuhiko、Nakata Masao、Hattori Noboru、Yamaguchi Hiroyuki、Fukuda Minoru、Nozawa Ryohei、Kakimi Kazuhiro、Oka Mikio
  • Journal Title: Journal of Thoracic Oncology Volume: 14 Issue: 12 Pages: 2071-2083
  • DOI: 10.1016/j.jtho.2019.08.008
  • NAID: 120006796543
  • Peer Reviewed / Open Access
• [Journal Article] Irreversible Electroporation Versus Radiofrequency Ablation: Comparison of Systemic Immune Responses in Patients With Hepatocellular Carcinoma. (2019)
  • Author(s): Sugimoto K, Kakimi K, Takeuchi H, Fujieda N, Saito K, Sato E, Sakamaki K, Moriyasu F, Itoi T.
  • Journal Title: J Vasc Interv Radiol Volume: 30 Issue: 6 Pages: 845-853
  • DOI: 10.1016/j.jvir.2019.03.002
  • Peer Reviewed
• [Journal Article] TCR Repertoire Analysis Reveals Mobilization of Novel CD8+ T Cell Clones Into the Cancer-Immunity Cycle Following Anti-CD4 Antibody Administration (2019)
  • Author(s): Aoki Hiroyasu、Ueha Satoshi、Shichino Shigeyuki、Ogiwara Haru、Hashimoto Shin-ichi、Kakimi Kazuhiro、Ito Satoru、Matsushima Kouji
  • Journal Title: Frontiers in Immunology Volume: 9 Pages: 3185-3185
  • DOI: 10.3389/fimmu.2018.03185
  • Peer Reviewed / Open Access
• [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] Reduced Neoantigen Expression Revealed by Longitudinal Multiomics as a Possible Immune Evasion Mechanism in Glioma. (2019)
  • Author(s): Nejo T, Matsushita H, Karasaki T, Nomura M, Saito K, Tanaka S, Takayanagi S, Hana T, Takahashi S, Kitagawa Y, Koike T, Kobayashi Y, Nagae G, Yamamoto S, Ueda H, Tatsuno K, Narita Y, Nagane M, Ueki K, Nishikawa R, Aburatani H, Mukasa A, Saito N, Kakimi K.
  • Journal Title: Cancer Immunol Res Volume: in press Issue: 7 Pages: 1148-1161
  • DOI: 10.1158/2326-6066.cir-18-0599
  • 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] High CCR4 expression in the tumor microenvironment is a poor prognostic indicator in lung adenocarcinoma. (2018)
  • Author(s): Karasaki T, Qiang G, Anraku M, Sun Y, Shinozaki-Ushiku A, Sato E, Kashiwabara K, Nagayama K, Nitadori JI, Sato M, Murakawa T, Kakimi K, Fukayama M, Nakajima J.
  • Journal Title: J Thorac Dis Volume: 10 Pages: 4741-4750
  • Peer Reviewed
• [Journal Article] Expression of multiple immune checkpoint molecules on T cells in malignant ascites from epithelial ovarian carcinoma (2018)
  • Author(s): Imai Yuichi、Hasegawa Kosei、Matsushita Hirokazu、Fujieda Nao、Sato Sho、Miyagi Etsuko、Kakimi Kazuhiro、Fujiwara Keiichi
  • Journal Title: Oncology Letters Volume: 15 Pages: 6457-6468
  • DOI: 10.3892/ol.2018.8101
  • Peer Reviewed / Open Access
• [Presentation] 非造影 MR 画像の位相的特徴づけによる前立腺癌と前立腺肥大症の鑑別の 視覚化 (2022)
  • Author(s): 白石 憲史郎, 井上 皓介, 辻 拓将, 廣瀬 裕大, 熊谷 仁, 古徳 純一
  • Organizer: 第124回日本医学物理学会学術大会
• [Presentation] 非造影 MR 画像の位相的特徴づけによる前立腺癌と前立腺肥大症の鑑別の 視覚化 (2022)
  • Author(s): 井上 皓介, 辻 拓将, 廣瀬 裕大, 熊谷 仁, 白石 憲史郎, 古徳 純一
  • Organizer: 第124回日本医学物理学会学術大会
• [Presentation] 解剖学的ドメイン知識を取り込んだ胸部Ｘ線画像分類 (2022)
  • Author(s): 辻 拓将, 平田 有紀奈, 楠瀬 賢也, 佐田 政隆, 熊谷 仁, 白石 憲史郎, 古徳 純一
  • Organizer: 第124回日本医学物理学会学術大会
• [Presentation] 乳がん腋窩リンパ節転移に対する術前化学療法奏効例への術後放射線療法（PMRT） (2022)
  • Author(s): 白石憲史郎
  • Organizer: 第60回日本癌治療学会学術集会
  • Invited
• [Presentation] Usefulness of Kampo in Radiaition Therapy (2022)
  • Author(s): 白石憲史郎
  • Organizer: 第60回日本癌治療学会学術集会
  • Invited
• [Presentation] 治療計画時と同じ条件で撮像した診断時PET/CT画像を用いた術前薬物療法後の高精度放射線治療 (2022)
  • Author(s): 白石憲史郎,北隅加菜子,熊谷 仁, 上原隆三, 近松 孝
  • Organizer: 第30回日本乳癌学会学術総会
• [Presentation] 乳房温存術後Sequential BoostとSimultaneous Integrated Boostの比較 (2022)
  • Author(s): 白石憲史郎,熊谷 仁, 上原隆三, 石田亜樹, 野元昭弘, 岩井良夫
  • Organizer: 日本放射線腫瘍学会第35回学術大会
• [Presentation] Postoperative breastradiotherapy using deformable image registration of initial PET-CT before NAC (2022)
  • Author(s): Shiraishi K
  • Organizer: 13th European Breast Cancer Conference (EBCC-13)
  • Int'l Joint Research
• [Presentation] III 期 NSCLC に CDDP+S-1 は PACIFIC 戦略の有 望レジメンになり得るか？ (SAMURAI study) (2022)
  • Author(s): 藤原慶一・丹澤盛・田中寿志・ 稲葉恵・中村純也・岸川孝之・ 中嶌賢尚・柴田和彦・幸山正・ 石田博雄・三角俊裕・白石憲史郎・ 松谷哲行・関順彦・Samurai Group
  • Organizer: 第 63 回日本肺癌学会学術集会
• [Presentation] Phase II study of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small cell lung cancer in Japan (SAMURAI study) (2022)
  • Author(s): Nakashima M , Tanzawa S , Tanaka H , Inaba M , Nakamura J , Shibata K, Kishikawa T, Fujiwara K, Kohyama T, Ishida H, Misumi T, Shiraishi K, Matsutani N, Seki N
  • Organizer: ESMO Asia Congress
  • Int'l Joint Research
• [Presentation] Capsule Networkを用いたOCTのAI画像診断. (2019)
  • Author(s): 三村 達哉, 辻 拓将, 溝田 淳, 廣瀬 裕大, 藤森 康平, 弘瀬 拓矢, 白石 憲史郎, 小林 毅範, 古徳 純一
  • Organizer: 第123回日本眼科学会総会
• [Presentation] 新しい体表面検出器システムを用いた Surface-IGRT における空間位置精度のファントム study. (2019)
  • Author(s): 上村亮平、川合智之、今大輔、熊谷仁、新井範一、白石憲史郎
  • Organizer: 第75回日本放射線技術学会総会学術大会
• [Presentation] Differentiation of brain tumors by characterization of non-contrast-enhanced MR images using persistent homology. (2019)
  • Author(s): Oyama A, Hiraoka Y, Obayashi I, Oba H, Sumida K, Furui S, Shiraishi K, Saikawa Y, Kumagai S, Kotoku J.
  • Organizer: 第117回日本医学物理学会学術大会
• [Presentation] Differentiation of high-grade glioma and brain metastases by using texture analysis on no-enhanced MR images. (2019)
  • Author(s): Saikawa Y, Shiraishi K, Kondo H, Oba H, Furui S, Oyama A, Kumagai S, Kobayashi T, Kotoku J.
  • Organizer: 第117回日本医学物理学会学術大会
• [Presentation] Classification of Optical Coherence Tomography images by Capsule Network. (2019)
  • Author(s): Tsuji T, Mimura T, Mizota A, Hirose Y, Fujimori K, Hirose T, Shiraishi K, Kobayashi T, Kotoku J.
  • Organizer: 第117回日本医学物理学会学術大会
• [Presentation] Adjuvant radiotherapy for primary squamous cell carcinoma of the breast. (2019)
  • Author(s): Ogita M, Shiraishi K, Chang T, Kawamori J, Takahashi W, Kiritoshi T, Yamashita H, Nakagawa K.
  • Organizer: ESTRO (European Society for Therapeutic Radiology and Oncology) 38
• [Presentation] Metal Artifact correction improves dose calculation of intensity modulated radiation therapy. (2019)
  • Author(s): Moriwaki H, Ikeda T, Kiyomiya T, Tajima H, Shiraishi K, Sakumi A.
  • Organizer: ESTRO (European Society for Therapeutic Radiology and Oncology) 38
• [Presentation] Mixed reality for interventional radiology: an intuitive real-time radiation visualization system. (2019)
  • Author(s): Takata T, Kondo H, Yamamoto M, Furui S, Kobayashi T, Shiraishi K, Oba H, Kotoku J.
  • Organizer: CIRSE 2019
• [Book] 放射線治療AIと外科治療AI (2020)
  • Author(s): 藤田 広志、有村 秀孝、諸岡 健一
  • Total Pages: 250
  • Publisher: オーム社
  • ISBN: 9784274225475
• [Remarks] 帝京大学医学部放射線科学講座
  • URL: http://teikyo-rad.com/
• [Remarks] 帝京大学大学院医療技術学研究科診療放射線学専攻医学物理グループ
  • URL: http://square.umin.ac.jp/teikyo-mp/index.html
• [Remarks] 東京大学医学部附属病院免疫細胞治療学講座講座
  • URL: http://immunotherapy.umin.jp/