Identification of biomarkers which is useful for predicting the efficacy and treatment selection of immune checkpoint inhibitors

• Project/Area Number: 18K15331
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Fukuoka University
• Principal Investigator: Yamada Teppei 福岡大学, 医学部, 講師 (20772718)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 免疫チェックポイント阻害剤 / がん免疫療法 / 腫瘍免疫 / 腫瘍微小環境 / バイオマーカー / HLAクラスI APM関連分子 / 胃癌

Outline of Final Research Achievements

In recent years, the therapeutic effects of immune checkpoint inhibitors (ICIs) have made a significant impact on the world, and their combination with chemotherapy has already appeared in clinical practice and is becoming a key drug for cancer pharmacotherapy. However, ICIs have some problems that need to be resolved urgently, including high drug costs, lack of sensitive biomarkers that can predict efficacy, and the risk of serious immune-related adverse events (irAEs).
In six related projects to advance this research agenda, we were able to evaluate the tumor microenvironment (TME) in tumor tissue and immune cells in the peripheral blood in patients with various carcinomas. And also, we could evaluate the association between these results and therapeutic outcomes.

Academic Significance and Societal Importance of the Research Achievements

次項に示す6つのプロジェクトの研究成果により、免疫チェックポイント阻害剤（ICI）による効果予測に有用なバイオマーカーの同定や、治療の有効性を高める治療戦略の選定、薬剤感受性の改善、薬剤耐性獲得への対策につながる研究を促進させるための重要な情報を提供できたと考えられ、これらの研究成果をさらに発展させることで国家の医療費の削減やICI治療を受ける患者さんのリスク軽減に直接寄与できる結果を得ることが可能になると考える。

Research Products

• [Int'l Joint Research] Department of Surgery/Massachusetts General Hospital/Harvard Medical School(米国)
• [Journal Article] A Pan-Histone Deacetylase Inhibitor Enhances the Antitumor Activity of B7-H3?Specific CAR T Cells in Solid Tumors (2021)
  • Author(s): Lei X, Ou Z, Yang Z, Zhong J, Zhu Y, Tian J, Wu J, Deng H, Lin X, Peng Y, Li B, He L, Tu Z, Chen W, Li Q, Liu N, Zhang H, Wang Z, Fang Z, Yamada T, Lv X, Tian T, Pan G, Wu F, Xiao L, Zhang L, Cai T, Wang X, Tannous BA, Li J, Kontos F, Ferrone S, Fan S.
  • Journal Title: Clinical Cancer Research Volume: 27 Issue: 13 Pages: 3757-3771
  • DOI: 10.1158/1078-0432.ccr-20-2487
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tumor Microenvironment Immune Response in Pancreatic Ductal Adenocarcinoma Patients Treated With Neoadjuvant Therapy (2021)
  • Author(s): Michelakos Theodoros、Cai Lei、Villani Vincenzo、Sabbatino Francesco、Kontos Filippos、Fernandez-del Castillo Carlos、Yamada Teppei、Taylor Martin S、Deshpande Vikram、Kurokawa Tomohiro、Ting David T、Hong Theodore S、Ryan David P、Wo Jennifer Y、Warshaw Andrew L、Lillemoe Keith D、Ferrone Soldano、Ferrone Cristina R
  • Journal Title: JNCI: Journal of the National Cancer Institute Volume: 113 Issue: 2 Pages: 182-191
  • DOI: 10.1093/jnci/djaa073
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A fast, simple, and cost-effective method of expanding patient-derived xenograft mouse models of pancreatic ductal adenocarcinoma (2020)
  • Author(s): Liu Zhenyang、Ahn Michael Ho-Young、Kurokawa Tomohiro、Ly Amy、Zhang Gong、Wang Fuyou、Yamada Teppei、Sadagopan Ananthan、Cheng Jane、Ferrone Cristina R.、Liss Andrew S.、Honselmann Kim C.、Wojtkiewicz Gregory R.、Ferrone Soldano、Wang Xinhui
  • Journal Title: Journal of Translational Medicine Volume: 18 Issue: 1 Pages: 255-255
  • DOI: 10.1186/s12967-020-02414-9
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Changes in Immunological Status in Patients With Metastatic Colorectal Cancer Treated With First-line Chemoimmunotherapy (2020)
  • Author(s): YAMADA TEPPEI、YOSHIDA YOICHIRO、MAEDA TOSHIKI、YOSHIMATSU GUMPEI、AISU NAOYA、YAMASHITA KANEFUMI、KOMONO AKIRA、KAJITANI RYUJI、MATSUMOTO YOSHIKO、NAGANO HIDEKI、NAITO KEIKO、YASUMOTO KOSEI、TAKIMOTO RISHU、KAMIGAKI TAKASHI、GOTO SHIGENORI、YOSHIMURA FUMIHIRO、SAKATA NAOAKI、KODAMA SHOHTA、HASEGAWA SUGURU
  • Journal Title: Anticancer Research Volume: 40 Issue: 8 Pages: 4763-4771
  • DOI: 10.21873/anticanres.14478
  • Peer Reviewed
• [Journal Article] Role of Tumor Associated Macrophages in the Clinical Course of Pancreatic Neuroendocrine Tumors (PanNETs). (2019)
  • Author(s): Cai L, Michelakos T, Deshpande V, Arora KS, Yamada T, Ting DT, Taylor MS, Fernandez-Del Castillo C, Warshaw AL, Lillemoe KD, Ferrone S, Ferrone CR
  • Journal Title: Clin Cancer Res. Volume: 25 Issue: 8 Pages: 2644-2655
  • DOI: 10.1158/1078-0432.ccr-18-1401
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Potential Role of HLA Class I Antigens in the Glycolytic Metabolism and Motility of Melanoma Cells. (2019)
  • Author(s): Silvia Peppicelli, Jessica Ruzzolini, Elena Andreucci, Francesca Bianchini, Filippos Kontos, Teppei Yamada, Soldano Ferrone and Lido Calorini
  • Journal Title: Cancers Volume: 11 Issue: 9 Pages: 1249-1249
  • DOI: 10.3390/cancers11091249
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Defective HLA class I antigen processing machinery in cancer (2018)
  • Author(s): Lei Cai, Theodoros Michelakos, Teppei Yamada, Song Fan, Xinhui Wang, Joseph H. Schwab, Cristina R. Ferrone, Soldano Ferrone
  • Journal Title: Cancer Immunol Immunother. Volume: 67 Pages: 999-1009
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 当院での切除不能進行・再発胃癌に対するNivolumab療法の現状 (2020)
  • Author(s): 山田 哲平、吉村 文博、野 陽介、田中 敬太、島岡 秀樹、槇 研二、吉田 陽一郎、長谷川 傑
  • Organizer: 第17回日本免疫治療学会
• [Presentation] 当院における切除不能進行・再発胃癌に対するNivolumab療法を使用した治療戦略 (2020)
  • Author(s): 山田 哲平、吉村 文博、野 陽介、田中 敬太、島岡 秀樹、槇 研二、吉田 陽一郎、長谷川 傑
  • Organizer: 第75回日本消化器外科学会定期学術総会
• [Presentation] 当院における切除不能進行・再発胃癌に対するNivolumab療法と今後の展望 (2020)
  • Author(s): 山田 哲平、吉村 文博、濵畑 圭佑、山内 皓介、平野 陽介、田中 敬太、島岡 秀樹、槇 研二、吉田 陽一郎、長谷川 傑
  • Organizer: 第45回日本外科系連合学会学術州会