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

2012 Fiscal Year Final Research Report

• 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
• Keywords: 腫瘍 / 遺伝子細胞療法 / 細胞傷害活性

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 Pages: 553-564
  • DOI: 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 Pages: 561-569
  • DOI: DOI:10.1016/j.imbio.2012.07.022
  • Peer Reviewed
• [Journal Article] Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4(+) Th cells cytotoxic by activating both perforin- and FasL-pathways (2012)
  • Author(s): Eshima K, Chiba S, Suzuki H, Kokubo K, Kobayashi H, Iizuka M, Iwabuchi K, Shinohara N
  • Journal Title: Immunol Lett Volume: 144 Pages: 7-15
  • DOI: 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 CS, Ogura H, Fujii S, Eshima K, Nakayama T, Taniguchi M, Hirata N, Ishimori N, Tsutsui H, Onoe K, Iwabuchi K
  • Journal Title: PLoS One Volume: 7 Pages: e30568
  • DOI: DOI:10.1371/journal.pone.0030568
  • Peer Reviewed
• [Journal Article] Thromboxane A2receptor 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 Pages: 700-707
  • DOI: 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 Pages: 33-38
  • DOI: DOI:10.1111/j.1346-8138.2011.01413.x
  • 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] 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
• [Remarks]
  • URL: http://web.med.kitasato-u.ac.jp/edures/immunol.html