Elucidation of molecular mechanism of T cell terminal differentiation lineage for cancer immunotherapy

• Project/Area Number: 17K07215
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Osaka University
• Principal Investigator: Fujiki Fumihiro 大阪大学, 医学系研究科, 特任准教授(常勤) (40456926)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ターミナルエフェクター / 癌免疫療法 / がん免疫療法 / メモリーT細胞 / ターミナルエフェクターT細胞 / 免疫学 / 癌

Outline of Final Research Achievements

Efficient induction of memory T cells are required for optimal anti-tumor immune response. In this study, we identified a novel gene responsible for terminal effector T cell differentiation. Overexpression of the gene in T cells attenuated the expression of CD62L, proliferation capacity, and the resistance to apoptosis. Furthermore, the knockdown of the gene restored them in terminal effector T cells. Thus, the gene should be a promising target for enhancing cancer immunotherapy.

Academic Significance and Societal Importance of the Research Achievements

近年、癌免疫療法は癌治療の一つとして急速に発展してきた。しかしながら、その効果は限定的であり、その理由の一つとして患者の癌細胞を攻撃する免疫細胞の「質」が低下していることが明らかとなっている。本研究では、この免疫細胞の「質」が低下する責任遺伝子を同定した。この成果は将来、より強力な癌免疫療法の開発につながると期待される。

Research Products

• [Int'l Joint Research] Antwerp University(ベルギー)
• [Journal Article] Reader-free ELISPOT assay for immuno-monitoring in peptide-based cancer vaccine immunotherapy (2020)
  • Author(s): Hayashi Sae、Imanishi Rin、Adachi Mayuko、Ikejima Sayaka、Nakata Jun、Morimoto Soyoko、Fujiki Fumihiro、Nishida Sumiyuki、Tsuboi Akihiro、Hosen Naoki、Nakajima Hiroko、Hasegawa Kana、Oka Yoshihiro、Sugiyama Haruo、Oji Yusuke
  • Journal Title: Biomedical Reports Volume: 12 Pages: 244-250
  • DOI: 10.3892/br.2020.1289
  • Peer Reviewed / Open Access
• [Journal Article] Immune adjuvant therapy using Bacillus Calmette-Guérin cell wall skeleton (BCG-CWS) in advanced malignancies: A phase 1 study of safety and immunogenicity assessments. (2019)
  • Author(s): Nishida S, Tsuboi A, Tanemura A, Ito T, Nakajima H, Shirakata T, Morimoto S, Fujiki F, Hosen N, Oji Y, Kumanogoh A, Kawase I, Oka Y, Azuma I, Morita S, Sugiyama H.
  • Journal Title: Medicine (Baltimore) Volume: 98 Issue: 33 Pages: e16771-e16771
  • DOI: 10.1097/md.0000000000016771
  • Peer Reviewed / Open Access
• [Journal Article] A phase I clinical study of a cocktail vaccine of Wilms’ tumor 1 (WT1) HLA class I and II peptides for recurrent malignant glioma (2018)
  • Author(s): Tsuboi A, Hashimoto N, Fujiki F, Morimoto S, Kagawa N, Nakajima H, Hosen N, Nishida S, Nakata J, Morita S, Sakamoto J, Oji Y, Oka Y, Sugiyama H
  • Journal Title: Cancer Immunology, Immunotherapy Volume: 68(2) Issue: 2 Pages: 331-340
  • DOI: 10.1007/s00262-018-2274-1
  • Peer Reviewed / Open Access
• [Journal Article] Extremely strong infiltration of WT1-specific CTLs into mouse tumor by the combination vaccine with WT1-specific CTL and helper peptides (2018)
  • Author(s): Nakata Jun、Nakajima Hiroko、Hayashibara Hiromu、Imafuku Kanako、Morimoto Soyoko、Fujiki Fumihiro、Motooka Daisuke、Okuzaki Daisuke、Hasegawa Kana、Hosen Naoki、Tsuboi Akihiro、Oka Yoshihiro、Kumanogoh Atsushi、Oji Yusuke、Sugiyama Haruo
  • Journal Title: Oncotarget Volume: 9 Issue: 89 Pages: 36029-36038
  • DOI: 10.18632/oncotarget.26338
  • Peer Reviewed
• [Journal Article] Efficient and Non-genotoxic RNA-Based Engineering of Human T Cells Using Tumor-Specific T Cell Receptors With Minimal TCR Mispairing (2018)
  • Author(s): Campillo-Davo Diana、Fujiki Fumihiro、Van den Bergh Johan M. J.、De Reu Hans、Smits Evelien L. J. M.、Goossens Herman、Sugiyama Haruo、Lion Eva、Berneman Zwi N.、Van Tendeloo Viggo
  • Journal Title: Frontiers in Immunology Volume: 9
  • DOI: 10.3389/fimmu.2018.02503
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity (2018)
  • Author(s): Morimoto Soyoko、Fujiki Fumihiro、Kondo Kenta、Nakajima Hiroko、Kobayashi Yoshiki、Inatome Miki、Aoyama Nao、Nishida Yuya、Tsuboi Akihiro、Oka Yoshihiro、Nishida Sumiyuki、Nakata Jun、Hosen Naoki、Oji Yusuke、Sugiyama Haruo
  • Journal Title: Oncotarget Volume: 9 Issue: 75 Pages: 34132-34141
  • DOI: 10.18632/oncotarget.26139
  • Peer Reviewed / Open Access
• [Journal Article] A versatile T cell-based assay to assess therapeutic antigen-specific PD-1-targeted approaches (2018)
  • Author(s): Versteven Maarten、Bergh Johan M.J. Van den、Broos Katrijn、Fujiki Fumihiro、Campillo-Davo Diana、De Reu Hans、Morimoto Soyoko、Lecocq Quentin、Keyaerts Marleen、Berneman Zwi、Sugiyama Haruo、Van Tendeloo Viggo F.I.、Breckpot Karine、Lion Eva
  • Journal Title: Oncotarget Volume: 9 Issue: 45 Pages: 27797-27808
  • DOI: 10.18632/oncotarget.25591
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] WT1 peptide-based immunotherapy for advanced thymic epithelial malignancies (2018)
  • Author(s): Oji Y、Inoue M、Takeda Y、Hosen N、Shintani Y、Kawakami M、Harada T、Murakami Y、Iwai M、Fukuda M、Nishida S、Nakata J、Nakae Y、Takashima S、Shirakata T、Nakajima H、Hasegawa K、Kida H、Kijima T、Morimoto S、Fujiki F、Tsuboi A、Morii E、Morita S、Sakamoto J、Kumanogoh A、Oka Y、Okumura M、Sugiyama H
  • Journal Title: International Journal of Cancer Volume: 142 Issue: 11 Pages: 2375-2382
  • DOI: 10.1002/ijc.31253
  • Peer Reviewed / Open Access
• [Journal Article] Combination Gemcitabine and WT1 Peptide Vaccination Improves Progression-Free Survival in Advanced Pancreatic Ductal Adenocarcinoma: A Phase II Randomized Study. (2018)
  • Author(s): Nishida S, Ishikawa T, Egawa S, Koido S, Yanagimoto H, Ishii J, Kanno Y, Kokura S, Yasuda H, Oba MS, Sato M, Morimoto S, Fujiki F, Eguchi H, Nagano H, Kumanogoh A, Unno M, Kon M, Shimada H, Ito K, Homma S, Oka Y, Morita S, Sugiyama H.
  • Journal Title: Cancer Immunol Res. Volume: 6 Issue: 3 Pages: 320-331
  • DOI: 10.1158/2326-6066.cir-17-0386
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia (2017)
  • Author(s): Anguille Sebastien、et al
  • Journal Title: Blood Volume: 130 Issue: 15 Pages: 1713-1721
  • DOI: 10.1182/blood-2017-04-780155
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Comparison of WT1-specific T cell responses in recurrent glioma patients received CTL + Helper peptide vaccine vs CTL peptide vaccine alone (2019)
  • Author(s): Fumihiro Fujiki, Akihiro Tsuboi, Soyoko Morimoto, Naoya Hashimoto, Miki Inatome, Yoshihiro Oka, Yusuke Oji, Haruo Sugiyama
  • Organizer: International Conference on WT1 Biology
  • Int'l Joint Research
• [Presentation] Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity and its application (2019)
  • Author(s): Soyoko Morimoto, Fumihiro Fujiki, Maarten Versteven, Kenta Kondo, Hiroko Nakajima, Yoshiki Kobayashi, Miki Inatome, Nao Aoyama, Yuya Nishida, Akihiro Tsuboi, Yoshihiro Oka, Yusuke Oji, Eva Lion, Haruo Sugiyama
  • Organizer: International Conference on WT1 Biology
  • Int'l Joint Research
• [Presentation] 再発脳腫瘍患者におけるWT1ヘルパーペプチド併用WT1ペプチドワクチン療法の免疫モニタリング解析 (2019)
  • Author(s): 藤木文博、坪井昭博、森本創世子、橋本直哉、稲留美希、中島博子、中田潤、保仙直毅、尾路祐介、岡芳弘、杉山治夫
  • Organizer: 第11回日本血液疾患免疫療法学会学術集会
• [Presentation] 癌抗原特異的T細胞受容体のfunctional avidity を効率よく正確に評価できるplatform細胞の作製とその応用例 (2019)
  • Author(s): 森本創世子、藤木文博、近藤健太、中島博子、中田潤、保仙直毅、橋井佳子、坪井昭博、岡芳弘、尾路祐介、杉山治夫
  • Organizer: 第11回日本血液疾患免疫療法学会学術集会
• [Presentation] 急性骨髄性白血病に対するWT1ワクチン療法の現状および今後の展望 (2019)
  • Author(s): 中田潤、中江吉希、川上学、森本創世子、中島博子、藤木文博、西田純幸、保仙直毅、坪井昭博、尾路祐介、岡芳弘、杉山治夫
  • Organizer: 第11回日本血液疾患免疫療法学会学術集会
• [Presentation] 脳腫瘍患者におけるWT1ヘルパーペプチド併用WT1ペプチドワクチン療法の免疫モニタリング解析 (2019)
  • Author(s): 森本創世子、坪井昭博、藤木文博、橋本直哉、稲留美希、中島博子、中田潤、保仙直毅、尾路祐介、岡芳弘、杉山治夫
  • Organizer: 第47回日本臨床免疫学会総会
• [Presentation] 癌抗原特異的 T 細胞受容体の functional avidity を効率よく正確に評価できる platform 細胞の作製 (2018)
  • Author(s): 森本創世子
  • Organizer: 第46回日本臨床免疫学会総会
• [Presentation] Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity (2018)
  • Author(s): Soyoko Morimoto
  • Organizer: 9th International Conference on WT1 in Human Neoplasia
  • Int'l Joint Research
• [Presentation] 切除不能進行膵癌に対するゲムシタビン併用HLA拘束性WT1ペプチドワクチン療法で誘導されたWT1特異的CTLの免疫学的機能解析 (2017)
  • Author(s): 森本創世子、西田純幸、他
  • Organizer: 第21回日本がん免疫学会総会