Identification of T cells that exhibit cytotoxic activity against tumor based on the single-cell gene expression profiles and control their function

• Project/Area Number: 15K18446
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Osaka University
• Principal Investigator: Morimoto Soyoko 大阪大学, 医学系研究科, 寄附講座助教 (10649023)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: single cell RT-PCR / WT1 specific CTLs / memory / WT1特異的CTL / single cell / TCR / single cell定量PCR

Outline of Final Research Achievements

Multiple gene-expression analysis using single-cell real-time PCR showed that WT1 specific effector-memory CTL (WT1-EM CTL) population from cancer patients could be divided into two groups: the “activated” and “quiescent” states and WT1-EM CTL in good responder turn from “activated (Group: A)” to “quiescent (Group: B)” after WT1 peptide vaccination. We further show that TCR avidity could have played an essential role in differentiation of self-antigen-reactive T cells.

Research Products

• [Journal Article] Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide. (2016)
  • Author(s): Oji Y, Hashimoto N, Tsuboi A, Murakami Y, Iwai M, Kagawa N, Chiba Y, Izumoto S, Elisseeva O, Ichinohasama R, Sakamoto J, Morita S, Nakajima H, Takashima S, Nakae Y, Nakata J, Kawakami M, Nishida S, Hosen N, Fujiki F, Morimoto S, Adachi M, Iwamoto M, Oka Y, Yoshimine T, Sugiyama H.
  • Journal Title: Int J Cancer. Volume: 139 Issue: 6 Pages: 1391-401
  • DOI: 10.1002/ijc.30182
  • Peer Reviewed / Open Access
• [Journal Article] Syndecan-4 as a biomarker to predict clinical outcome for glioblastoma multiforme treated with WT1 peptide vaccine (2016)
  • Author(s): Takashima S, Oka Y, Fujiki F, Morimoto S, Nakajima H, Nakae Y, Nakata J, Nishida S, Hosen N, Tatsumi N, Mizuguchi K, Hashimoto N, Oji Y, Tsuboi A, Kumanogoh A, Sugiyama H
  • Journal Title: Future Sci OA Volume: FSO96 Issue: 4
  • DOI: 10.4155/fsoa-2015-0008
  • Peer Reviewed / Open Access
• [Journal Article] An essential role of the avidity of T-cell receptor in differentiation of self-antigen-reactive CD8+ T cells (2016)
  • Author(s): Kondo K, Fujiki F, Nakajima H, Yatsukawa E, Morimoto S, Tatsumi N, Nishida S, Nakata J, Oka Y, Tsuboi A, Hosen N, Oji Y, Sugiyama H
  • Journal Title: Journal of Immunotherapy Volume: 39 Issue: 3 Pages: 127-139
  • DOI: 10.1097/cji.0000000000000114
  • Peer Reviewed / Open Access
• [Journal Article] A Zbtb7a proto-oncogene as a novel target for miR-125a. (2016)
  • Author(s): Hojo N, Tatsumi N, Moriguchi N, Matsumura A, Morimoto S, Nakata J, Fujiki F, Nishida S, Nakajima H, Tsuboi A, Oka Y, Hosen N, Hayashi S, Sugiyama H, Oji Y.
  • Journal Title: Molecular Carcinogenesis Volume: - Issue: 12 Pages: 1-9
  • DOI: 10.1002/mc.22446
  • Peer Reviewed / Open Access
• [Journal Article] Glycosylation Status of CD43 Protein Is Associated with Resistance of Leukemia Cells to CTL-Mediated Cytolysis. (2016)
  • Author(s): Hasegawa K, Tanaka S, Fujiki F, Morimoto S, Nakano K, Kinoshita H, Okumura A, Fujioka Y, Urakawa R, Nakajima H, Tatsumi N, Nakata J, Takashima S, Nishida S, Tsuboi A, Oka Y, Oji Y, Miyoshi E, Hirata T, Kumanogoh A, Sugiyama H, Hosen N.
  • Journal Title: PLoS One Volume: 11 Issue: 3 Pages: e0152326-e0152326
  • DOI: 10.1371/journal.pone.0152326
  • Peer Reviewed / Open Access
• [Journal Article] An immunocompetent mouse model for MLL/AF9 leukemia reveals the potential of spontaneous cytotoxic T-cell response to an antigen expressed in leukemia cells (2015)
  • Author(s): Kana Hasegawa, Satomi Tanaka, Fumihiro Fujiki, Soyoko Morimoto, Hiroko Nakajima, Naoya Tatsumi, Jun Nakata, Satoshi Takashima, Sumiyuki Nishida, Akihiro Tsuboi, Yoshihiro Oka, Yusuke Oji, Atsushi Kumanogoh, Haruo Sugiyama, Naoki Hosen
  • Journal Title: PLoS ONE Volume: 10 Issue: 12 Pages: e0144594-e0144594
  • DOI: 10.1371/journal.pone.0144594
  • Peer Reviewed / Open Access
• [Journal Article] Identification of a Novel C-Terminal Truncated WT1 Isoform with Antagonistic Effects against Major WT1 Isoforms. (2015)
  • Author(s): Tatsumi N, Hojo N, Sakamoto H, Inaba R, Moriguchi N, Matsuno K, Fukuda M, Matsumura A, Hayashi S, Morimoto S, Nakata J, Fujiki F, Nishida S, Nakajima H, Tsuboi A, Oka Y, Hosen N, Sugiyama H, Oji Y.
  • Journal Title: PLoS One Volume: 10 Issue: 6 Pages: e0130578-e0130578
  • DOI: 10.1371/journal.pone.0130578
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 進行膵癌に対するゲムシタビン併用WT1ワクチン療法ランダム化第II創臨床試験：臨床効果と抗原特異的免疫反応の評価 (2016)
  • Author(s): 西田 純幸、石川 剛、江川 新一、小井戸 薫雄、森本 創世子、石井 淳、菅野 良秀、柳本 泰明、大庭 真梨、古倉 聡、本間 定、島田 英昭、森田 智視、岡 芳弘、杉山 治夫
  • Organizer: 第20回日本がん免疫学会総会
  • Place of Presentation: 大阪国際交流センター（大阪府大阪市）
  • Year and Date: 2016-07-27
• [Presentation] Randamized phase II stuy of WT1 peptide vaccine plus gemcitabine for advanced pancreatic ductal adenocarcinoma (PDAC): Clinical efficacy and immune response (2016)
  • Author(s): Sumiyuki Nishida, Takeshi Ishikawa, Satoshi Kokura, Shinichi Egawa, Shigeo Koido, Hiroaki Yasuda, Hiroaki Yanagimoto, Jun Ishii, Yoshihide Kanno, Mari Saito Oba, Maho Sato, Soyoko Morimoto, Hidetoshi Eguchi, Hiroaki Nagano, Sadamu Homma, Yoshihiro Oka, Satoshi Morita, Haruo Sugiyama
  • Organizer: 2016 ASCO Annual Meeting
  • Place of Presentation: シカゴ（米国）
  • Year and Date: 2016-06-03
  • Int'l Joint Research