Role of FDG-PET as therapeutic predictive marker of anti-PD-1 antibody in lung cancer

• Project/Area Number: 17K10433
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Saitama Medical University (2018-2019); Gunma University (2017)
• Principal Investigator: Kaira Kyoichi 埼玉医科大学, 医学部, 教授 (40400783)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: PD-L1 / 免疫療法 / 肺癌 / GLUT1 / HIF-1 / FDG-PET / 糖代謝 / 低酸素 / HIF-1α / PET / 腫瘍免疫 / がん免疫 / 放射線 / 核医学 / 呼吸器 / 腫瘍

Outline of Final Research Achievements

In experimental study, cell lines with high and low PD-L1 expression were correlated with the expression of GLUT1 and HIF-1. The trend of high HIF-1 expression was observed in cell line with high PD-L1, compared with that of low PD-L1. The immunohistochemical analysis using 450 tumor specimens with resected lung cancer revealed that the uptake of FDG was closely associated with PD-L1 expression, and there was significantly relationship between PD-L1 expression and GLUT1 and HIF-1. But, there was not association between tumor infiltrative lymphocytes and FDG uptake. Actually, we conducted the exploratory clinical trial to investigate the therapeutic significance of FDG-PET after anti PD-1/PD-L1 antibodies administration in patients with advanced non-small cell lung cancer. This study is ongoing now.

Academic Significance and Societal Importance of the Research Achievements

抗PD-1・PD-L1抗体の確立したバイオマーカーはなく、現状では腫瘍内PD-L1発現を治療効果予測マーカーの目安にしている。しかし、腫瘍組織内のPD-L1発現を正確に評価することである。そこで、PD-L1発現と関連性のある糖代謝マーカーであるFDG-PETでダイナミックにPD-L1発現の変化をとらえることができれば、免疫療法の効果を予測するのに有望である。本研究はその先駆けになる研究であり、今後の展開が期待されるものと思われる。

Research Products

• [Journal Article] Prognostic Significance of Tumor Immunity in Surgically Resected Pulmonary Pleomorphic Carcinoma (2020)
  • Author(s): Kaira K, Shimizu K, Endoh H, Imaizumi K, Kamiyoshihara M, Sugano M, Kawashima O, Tanaka S, Fujita A, Imai H, Kogure Y, Oyama T, Asao T, Shirabe K.
  • Journal Title: Anticancer Res Volume: 40 Issue: 1 Pages: 261-269
  • DOI: 10.21873/anticanres.13948
  • Peer Reviewed / Open Access
• [Journal Article] Potential of FDG-PET as Prognostic Significance after anti-PD-1 Antibody against Patients with Previously Treated Non-Small Cell Lung Cancer (2020)
  • Author(s): Hashimoto K., Kaira K., Yamaguchi O., Mouri A., Shiono A., Miura Y., Murayama Y., Kobayashi K., Kagamu H., Kuji I.
  • Journal Title: J Clin Med Volume: 9 Issue: 3 Pages: 725-735
  • DOI: 10.3390/jcm9030725
  • Peer Reviewed / Open Access
• [Journal Article] Fluorodeoxyglucose Uptake Is Associated With Low Tumor-Infiltrating Lymphocyte Levels in Patients With Small Cell Lung Cancer (2019)
  • Author(s): Kasahara N, Kaira K, Yamaguchi K, Masubuchi H, Tsurumaki H, Hara K, Koga Y, Sakurai R, Higuchi T, Handa T, Oyama T, Yokobori T, Shimizu K, Asao T, Hisada T.
  • Journal Title: Lung Cancer Volume: 134 Pages: 180-186
  • DOI: 10.1016/j.lungcan.2019.06.009
  • Peer Reviewed / Open Access
• [Journal Article] Expression of amino acid transporter (LAT1 and 4F2hc) in pulmonary pleomorphic carcinoma. (2019)
  • Author(s): Kaira K, Kawashima O, Endoh H, Imaizumi K, Goto Y, Kamiyoshihara M, Sugano M, Yamamoto R, Osaki T, Tanaka S, Fujita A, Imai H, Kogure Y, Seki Y, Shimizu K, Mogi A, Shitara Y, Oyama T, Kanai Y, Asao T.
  • Journal Title: Hum Pathol. Volume: 84 Pages: 142-149
  • DOI: 10.1016/j.humpath.2018.09.020
  • Peer Reviewed
• [Journal Article] Prognostic significance of PD-L1 expression and tumor infiltrating lymphocytes in large cell neuroendocrine carcinoma of lung. (2018)
  • Author(s): Ohtaki Y, Kaira K, Atsumi J, Nagashima T, Kawashima O, Ibe T, Kamiyoshihara M, Onozato R, Fujita A, Yazawa T, Sugano M, Iijima M, Nakazawa S, Obayashi K, Kosaka T, Yajima T, Kuwano H, Shirabe K, Mogi A, Shimizu K.
  • Journal Title: Am J Transl Res. Volume: 15 Pages: 3243-3253
  • Peer Reviewed / Open Access
• [Journal Article] Correlation of tumor-related immunity with 18F-FDG-PET in pulmonary squamous-cell carcinoma. (2018)
  • Author(s): Kasahara N, Kaira K, Bao P, Higuchi T, Arisaka Y, Erkhem-Ochir B, Sunaga N, Ohtaki Y, Yajima T, Kosaka T, Oyama T, Yokobori T, Asao T, Nishiyama M, Tsushima Y, Kuwano H, Shimizu K, Mogi A.
  • Journal Title: Lung Cancer Volume: 119 Pages: 71-77
  • DOI: 10.1016/j.lungcan.2018.03.001
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 既治療進行非小細胞肺癌に対する抗PD-1抗体単剤の予後予測におけるFDG集積の役割 (2020)
  • Author(s): 橋本 康佑、解良恭一他
  • Organizer: 第60回日本呼吸器学会学術講演会