Conference of cytotoxicity to tumor antigen specific CD4+helper T cells and the analyses of its anti-tumor activity

• Project/Area Number: 22501024
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor immunology
• Research Institution: Kitasato University
• Principal Investigator: ESHIMA Koji 北里大学, 医学部, 講師 (30327324)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 腫瘍 / 遺伝子細胞療法 / 細胞傷害活性 / 細胞傷害性T細胞 / 抗腫瘍免疫 / 細胞療法 / 遺伝子療法 / 癌 / 遺伝子導入 / 転写因子 / Eomesodermin

Research Abstract

In this study, we examined whether non-cytocidal helper T cells could be converted into cytotoxic T lymphocytes (CTL) via gene transferring, in order to investigate the possibility that conference of cytotoxicity to tumor antigen specific helper T cells could be utilized to eradicate tumors. It was suggested transfection of either one gene of the two T-box molecules, Eomesodermin and T-bet, could activate both of the two cytolytic pathways of CD8+CTLs and conferred the cytolytic activity to helper T cells. Microarray analyses revealed that Eomes could induce several other CTL-specific genes which may be involved in shaping characteristics of CD8+CTLs. Currently, Eomes-Tg line is being established for further detailed analyses for the clinical use of this protocol for tumor treatment.

Research Products

• [Journal Article] Angiotensin II type 1A receptor signaling facilitates tumor metastasis formation through P-selectin-mediated interaction of tumor cells with platelets and endothelial cells (2013)
  • Author(s): Amano H, Ito Y, Ogawa F, Eshima K, Suzuki T, Oba K, Matsui Y, Kato S, Fukui T, Nakamura M, Kitasato H, Fukamizu A, Majima M
  • Journal Title: Am J Pathol Volume: 182(2) Issue: 2 Pages: 553-64
  • DOI: 10.1016/j.ajpath.2012.10.026
  • Peer Reviewed
• [Journal Article] Natural killer T cells are required for lipopolysaccharide-mediated enhancement of atherosclerosis in apolipoprotein E-deficient mice (2013)
  • Author(s): Andoh Y, Ogura H, Satoh M, Shimano K, Okuno H, Fujii S, Ishimori N, Eshima K, Tamauchi H, Otani T, Nakai Y, Van Kaer L, Tsutsui H, Onoe K, Iwabuchi K
  • Journal Title: Immunobiology Volume: 218 Issue: 4 Pages: 561-569
  • DOI: 10.1016/j.imbio.2012.07.022
  • Peer Reviewed
• [Journal Article] Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4+ Th celss cytotoxic by activating both perforin-nad FasL-pathways (2012)
  • Author(s): Eshima, K, et al
  • Journal Title: Immunol Lett Volume: 144 Issue: 1-2 Pages: 7-15
  • DOI: 10.1016/j.imlet.2012.02.013
  • Peer Reviewed
• [Journal Article] Type II NKT cells stimulate diet-induced obesity by mediating adipose tissue inflammation, steatohepatitis and insulin resistance (2012)
  • Author(s): Satoh, M., Andoh, Y., Clingan, S. C., Ogura, H., Fujii, S., Nakayama, T., Taniguchi, M., Hirata, N., Ishimori, N., Tsutsui, H., Onoe, K. Iwabuchi, K
  • Journal Title: PLoS ONE Volume: 7(2) Issue: 2 Pages: 1-12
  • DOI: 10.1371/journal.pone.0030568
  • NAID: 120004043739
  • Peer Reviewed
• [Journal Article] Thromboxane A_2 receptor signaling facilitates tumor colonization through P-selectin-mediated interaction of tumor cells with platelets and endothelial cells (2012)
  • Author(s): Matsui Y, Amano H, Ito Y, Eshima K, Suzuki T, Ogawa F, Iyoda A, Satoh Y, Kato S, Nakamura M, Kitasato H, Narumiya S, Majima M
  • Journal Title: Cancer Sci Volume: 103(4) Issue: 4 Pages: 700-7
  • DOI: 10.1111/j.1349-7006.2012.02200.x
  • Peer Reviewed
• [Journal Article] Nestin-positive hair follicle pluripotent stem cells can promote regeneration of impinged peripheral nerve injury (2012)
  • Author(s): Amoh Y, Aki R, Hamada Y, Niiyama S, Eshima K, Kawahara K, Sato Y, Tani Y, Hoffman RM, Katsuoka K
  • Journal Title: Dermatol Volume: 39 Issue: 1 Pages: 33-38
  • DOI: 10.1111/j.1346-8138.2011.01413.x
  • NAID: 10031184822
  • Peer Reviewed
• [Presentation] Spontaneous increase of Gr-1+/CD11b+cells in alymphoplasia mouse lacking functional NF-κB-inducing Kinase. (2012)
  • Author(s): 江島 耕二
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-02
• [Presentation] NF-κB-inducing kinase in non-hematopoietic cells is required for maintenance of normal number of γδ T cells in periphery (2012)
  • Author(s): 江島 耕二
  • Organizer: 第22回 KTCC (Kyoto T cell Conference)
  • Place of Presentation: 京都
  • Year and Date: 2012-07-07
• [Presentation] On the role of T-box family molecules in the activation of two cytolytic pathways (2011)
  • Author(s): 江島 耕二
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-27
• [Presentation] On the role of T-box family molecules in the activation of two cytolytic pathways (2011)
  • Author(s): 江島耕二, 千葉紗由利、佐藤雅、篠原信賢, 岩渕和也
  • Organizer: 第40回日本免疫学会学術
  • Place of Presentation: 千葉市
  • Year and Date: 2011-11-27
• [Presentation] Ectopic expression of T-box transcription factor, Eomesodermin, renders CD4+ Th2 cells cytotoxic by activating both perforin/granzyme- and FasL pathway. (2010)
  • Author(s): Koji Eshima
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-23
• [Presentation] Ectopic expression of T-box transcription factor, Eomesodermin, renders CD4^+ Th2 cells cytotoxic by activating both perforin/granzyme-and FasL pathways. (2010)
  • Author(s): 江島耕二
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸ポートピアホテル、神戸国際展示場(兵庫)
  • Year and Date: 2010-08-23
• [Presentation] Spontaneous increase of Gr-1+/CD11b+ cells in alymphoplasia mouse lacking functional NF-kB-inducing Kinase.
  • Author(s): 江島耕二
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸市
• [Presentation] NF-kB-inducing kinase in non-hematopoietic cells is required for maintenance of normal number of gd T cells in periphery.
  • Author(s): 江島耕二
  • Organizer: 第22回 KTCC (Kyoto T cell Conference)
  • Place of Presentation: 京都市
• [Remarks]
  • URL: http://web.med.kitasato-u.ac.jp/edures/immunol.html
• [Remarks] 北里大学医学部免疫学教室
  • URL: http://web.med.kitasato-u.ac.jp/edures/immunol.html
• [Remarks]
  • URL: http://web.med.kitasato-u.ac.jp/edures/immunol.html
• [Remarks]
  • URL: http://web.med.kitasato-u.ac.jp/edures/immunol.html