analysis of cancer immune reaction by irradiation

• Project/Area Number: 18K07740
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: Shun-Ichiro Kageyama 国立研究開発法人国立がん研究センター, 東病院, 医員 (60644979)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 放射線治療 / 食道癌 / STING / PD-L1 / 免疫チェックポイント / Radiation / Esophageal Cancer / Type I interferon / 放射線 / 免疫 / RNA seq / がん免疫療法 / がん免役 / JAK-STAT

Outline of Final Research Achievements

We identified a Type I interferon-dependent immune response, including PD-L1 and MHC class I, by X-ray irradiation of 30 Gy / 10 fr on esophageal cancer cell lines by RNA sequence.
Furthermore, we established gene knockout cell line and revealed that this immune response is caused by positive feedback of the STING-Type I IFN-STAT1-IRF1 cascade. Furthermore, it was clarified that this pathway-dependent induction of human PBMC infiltration into cancer cells.

Academic Significance and Societal Importance of the Research Achievements

放射線治療に免疫チェックポイント阻害剤を併用する試みは現在世界中で行われており、今後放射線治療の主座になることが予測されている。現在その効果は唯一肺非小細胞癌でのみ立証されているが、2/3が再発するのが現状である。このため、バイオマーカー確立や更なる治療精液向上の妙の併用治療等を検証するために、放射線によるがん免疫応答誘導の分子メカニズムを解明することは必須である。
本研究は放射線によるがん免疫誘導、type Iインターフェロン誘導から周囲の免疫細胞誘導まで一連のカスケードを明らかにしており、今後の放射線治療の向上に役立つ知見を提供する。

Research Products

• [Journal Article] Identification of the mutation signature of the cancer genome caused by irradiation (2021)
  • Author(s): Kageyama SI, Junyan D, Hojo H, Motegi A, Nakamura M, Tsuchihara K, Akimoto T.
  • Journal Title: Radiother Oncol. Volume: 155 Pages: 10-16
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Differences in failure patterns according to the EGFR mutation status after proton beam therapy for early stage non-small cell lung cancer. (2020)
  • Author(s): Nakamura M, Kageyama SI, Udagawa H, Zenke Y, Yoh K, Niho S, Hojo H, Motegi A, Kirita K, Matsumoto S, Goto K, Akimoto T.
  • Journal Title: Radiother Oncol Volume: 149 Pages: 14-17
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TENERGY: multicenter phase II study of Atezolizumab monotherapy following definitive Chemoradiotherapy with 5-FU plus Cisplatin in patients with unresectable locally advanced esophageal squamous cell carcinoma. (2020)
  • Author(s): Bando H, Kotani D, Tsushima T, Hara H, Kadowaki S, Kato K, Chin K, Yamaguchi K, Kageyama SI, Hojo H, Nakamura M, Tachibana H, Wakabayashi M, Fukutani M, Togashi Y, Fuse N, Nishikawa H, Kojima T.
  • Journal Title: BMC Cancer. Volume: 20 Pages: 336-336
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enhanced tumor response to radiotherapy after PD-1 blockade in metastatic gastric cancer. (2020)
  • Author(s): Sasaki A, Nakamura Y, Togashi Y, Kuno H, Hojo H, Kageyama SI, Nakamura N, Takashima K, Kadota T, Yoda Y, Mishima S, Sawada K, Kotani D, Kawazoe A, Kuboki Y, Taniguchi H, Kojima T, Doi T, Yoshino T, Yano T, Kobayashi T, Akimoto T, Nishikawa H, Shitara K.
  • Journal Title: Gastric Cancer. Volume: 23 Pages: 893-903
  • NAID: 40022329655
  • Peer Reviewed / Open Access / Int'l Joint Research