Analysis of immune response induced by radiotherapy in non-small cell lung cancer

• Project/Area Number: 20K17207
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Tohoku University
• Principal Investigator: Tsukita Yoko 東北大学, 大学病院, 助教 (50822566)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
• Keywords: 非小細胞肺癌 / 免疫療法 / 肺癌

Outline of Research at the Start

癌治療の柱の一つになっている免疫療法の有効性をさらに高める新たな治療法の開発は喫緊の課題である。現在、当院では未治療進行非小細胞肺癌患者を対象として、標準薬物療法（免疫療法＋殺細胞性抗癌剤）開始前に放射線姑息照射を施行することの有用性を検討する臨床試験を施行中である。この臨床試験で採取した治療前後の血液検体を用いて免疫細胞の種類、T細胞受容体の多様性、血漿中のインターフェロン・サイトカインなどを解析し、放射線照射がもたらす免疫応答への効果を解明する。

Outline of Final Research Achievements

Our objective was to elucidate the immune response in untreated advanced non-small cell lung cancer patients who underwent radiotherapy prior to initiation of immunotherapy plus cytotoxic agents. Peripheral blood mononuclear cells, cytokines and damage-associated molecular patterns in plasma before and after the treatment were examined in 13 patients who received radiotherapy. It was not possible to identify any factors that showed statistically or clinically significant changes by radiotherapy.
A comparison of 13 patients in the response group with 6 patients in the non-response group showed that NK cells, PD-1 positive Tim-3 positive CD4 positive T cells and CXCL10 in the pretreatment blood were significantly elevated in the response group. We found the combination of these three factors may be a more useful predictive biomarker in clinical practice.

Academic Significance and Societal Importance of the Research Achievements

未治療進行非小細胞肺癌において、免疫療法と殺細胞性抗癌剤との併用療法の効果予測となりうる因子を同定した。組織ではなく血液を使用することでより低侵襲に治療効果を予測できれば、肺癌患者の治療選択に貢献できると考える。

Research Products

• [Journal Article] First-line therapy in non-small cell lung cancer patients with EGFR activating mutations: a consideration of the clinical position of osimertinib based on the subset of Japanese patients in the FLAURA study. (2022)
  • Author(s): Yoko Tsukita, Akira Inoue
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 52 Issue: 5 Pages: 405-410
  • DOI: 10.1093/jjco/hyac012
• [Journal Article] Intensity-modulated radiation therapy with concurrent chemotherapy followed by durvalumab for stage III non-small cell lung cancer: A multi-center retrospective study. (2021)
  • Author(s): Tsukita Y, Yamamoto T, Mayahara H, Hata A, Takeda Y, Nakayama H, Tanaka S, Uchida J, Usui K, Toyoda T, Tamiya M, Morimoto M, Oya Y, Kodaira T, Miyauchi E, Jingu K, Sugiura H.
  • Journal Title: Radiother Oncol. Volume: 160 Pages: 266-272
  • DOI: 10.1016/j.radonc.2021.05.016
  • Peer Reviewed / Open Access
• [Journal Article] Immunotherapy-related hepatitis and thrombocytopaenia induced by the very low dose of only 90 mg of atezolizumab (2020)
  • Author(s): Yoko Tsukita, Eisaku Miyauchi, Masahide Fukudo, Takaaki Sasaki, Masakazu Ichinose
  • Journal Title: European journal of cancer Volume: 133 Pages: 22-24
  • DOI: 10.1016/j.ejca.2020.04.008
  • Peer Reviewed
• [Presentation] 非小細胞肺癌に対する殺細胞性抗癌剤・免疫チェックポイント阻害薬併用療法の効果予測因子の探索 (2023)
  • Author(s): 木村望、突田容子、渋谷里紗、宮内栄作、他4名
  • Organizer: 第63回日本呼吸器学会学術講演会
• [Presentation] A retrospective study of chemoradiotherapy with intensity-modulated radiotherapy for unresectable stage III NSCLC (2021)
  • Author(s): Yoko Tsukita, Takaya Yamamoto, Eisaku Miyauchi, Hiroshi Mayahara, Akito Hata, Yuichiro Takeda, Hidetsugu Nakayama, Satoshi Tanaka, Junji Uchida, Kazuhiro Usui, Tatsuya Toyoda, Motohiro Tamiya, Masahiro Morimoto, Yuko Oya, Takeshi Kodaira, Keiichi Jingu, Hisatoshi Sugiura
  • Organizer: 第18回日本臨床腫瘍学会学術集会