The effects of NKT cell-mediated immunotherapy by IDO inhibitor in mouse lung metastasis model

• Project/Area Number: 26860376
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Fujita Health University (2016); Suzuka University of Medical Science (2014-2015)
• Principal Investigator: Hoshi Masato 藤田保健衛生大学, 医療科学部, 講師 (40633996)
• Research Collaborator: SEISHIMA Mitsuru ; SAITO Kuniaki ; ITO Hiroyasu ; HARA Akira
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: インドールアミン酸素添加酵素1 / インドールアミン酸素添加酵素2 / トリプトファン代謝産物 / B16F10細胞 / 抗腫瘍効果 / 細胞免疫療法 / ＩＤＯ１ / ＩＤＯ２ / Ｂ１６Ｆ１０ / IDO1 / IDO2 / B16F10 / α－ガラクトシルセラミド / トリプトファン代謝 / １－MT / ＩＤＯ / Ｂ１６細胞 / α-ガラクトシルセラミド / トリプタファン代謝 / 1-metyl-D-tryptophan / 1-metyl-L-tryptophan

Outline of Final Research Achievements

The role of indoleamine 2,3-dioxygenase (Ido) in the L-tryptophan (Trp)-kynurenine (Kyn) pathway after lung metastasis model by injecting B16F10 cells was investigated. We used α-GalCer administrated mice of wild type (WT), IDO1 KO, IDO2 KO, and mice treated with 1-methyl-D or L-tryptophan (D or L-1MT), an inhibitor of Ido1 or Ido2 respectively, to study the importance of Trp-Kyn pathway metabolites.
The levels of Ido1 and Ido2 mRNA and protein expression in the lung from WT mice were significantly higher than those from non-injected WT mice. The anti-tumor effect in the lung from IDO1 KO mice or L-1MT treated mice was markedly improved compared to that in WT mice, IDO2 KO mice, and D-1MT treated mice. Moreover, the levels of Trp metabolites in lung from IDO1 KO mice or L-1MT treated mice was significantly decreased compared to that in lung from WT mice, IDO2 KO mice, and D-1MT treated mice.

Research Products

• [Journal Article] Absence of kynurenine 3-monooxygenase reduces mortality of acute viral myocarditis in mice (2017)
  • Author(s): Kubo H, Hoshi M, Mouri A, Tashita C, Yamamoto Y, Nabeshima T, Saito K.
  • Journal Title: IMMUNOLOGY LETTERS Volume: 181 Pages: 94-100
  • DOI: 10.1016/j.imlet.2016.11.012
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Inhibition of indoleamine 2,3-dioxygenase 1 expression alters immune response in colon tumor microenvironment in mice. (2015)
  • Author(s): Takamatsu M, Hirata A, Ohtaki H, Hoshi M, Ando T, Ito H, Hatano Y, Tomita H, Kuno T, Saito K, Seishima M, Hara A.
  • Journal Title: Cancer Sci. Volume: 106(8) Issue: 8 Pages: 1008-15
  • DOI: 10.1111/cas.12705
  • NAID: 120005767026
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Early microlesion of viral encephalitis confirmed by galectin-3 expression after a virus inoculation. (2015)
  • Author(s): Kobayashi K, Niwa M, Hoshi M, Saito K, Hisamatsu K, Hatano Y, Tomita H, Miyazaki T, Hara A.
  • Journal Title: Neuroscience letters. Volume: 592 Pages: 107-112
  • DOI: 10.1016/j.neulet.2015.02.061
  • Peer Reviewed / Open Access
• [Journal Article] Blockade of indoleamine 2,3-dioxygenase reduces mortality from peritonitis and sepsis in mice by regulating functions of CD11b+ peritoneal cells. (2014)
  • Author(s): Hoshi M, Osawa Y, Ito H, Ohtaki H, Ando T, Takamatsu M, Hara A, Saito K, Seishima M.
  • Journal Title: Infect Immun. Volume: 82(11) Issue: 11 Pages: 4487-95
  • DOI: 10.1128/iai.02113-14
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Kynurenine production mediated by indoleamine 2, 3-dioxygenase aggravates liver injury in HBV-specific CTL-induced fulminant hepatitis (2014)
  • Author(s): Ohtaki H, Ito H, Ando K, Ishikawa T, Hoshi M, Ando T, Takamatsu M, Hara A, Moriwaki H, Saito K, Seishima M
  • Journal Title: Biochim Biophys Acta Volume: 1842(9) Issue: 9 Pages: 1464-71
  • DOI: 10.1016/j.bbadis.2014.04.015
  • Peer Reviewed
• [Journal Article] Indoleamine 2,3-dioxygenase 1 is upregulated in activated microglia in mice cerebellum during acute viral encephalitis (2014)
  • Author(s): Taguchi A, Niwa M, Hoshi M, Saito K, Masutani T, Hisamatsu K, Kobayashi K, Hatano Y, Tomita H, Hara A
  • Journal Title: Neurosci Lett Volume: 3564 Pages: 120-5
  • DOI: 10.1016/j.neulet.2014.01.051
  • Peer Reviewed
• [Presentation] マウス致死性敗血症モデルにおけるインドールアミン酸素添加酵素の役割について (2016)
  • Author(s): 星 雅人 久保 緋紗子 毛利 彰宏 勅使河原 知明 山菅 和可奈 和田 直也 山本 康子 鍋島 俊隆 齋藤 邦明
  • Organizer: 第37回日本トリプトファン研究会学術集会
  • Place of Presentation: 東京農業大学、東京都世田谷区
  • Year and Date: 2016-12-10
• [Presentation] Absence of kynurenine 3-monooxygenase reduces mortality of acute viral myocarditis in mice (2016)
  • Author(s): 久保 緋紗子 星 雅人 毛利 彰宏 勅使河原 知明 山菅 和可奈 和田 直也 山本 康子 鍋島 俊隆 齋藤 邦明
  • Organizer: 第37回日本トリプトファン研究会学術集会
  • Place of Presentation: 東京農業大学、東京都世田谷区
  • Year and Date: 2016-12-10
• [Presentation] A rapid and highly sensitive method to evaluate the quinolinic acid using recombinant enzymes with HPLC-Fluorescence detection (2015)
  • Author(s): Hidetsugu Fujigaki, Akiko Sakamoto-Morise, Suwako Fujigaki, Kanako Hirabayashi-Takahashi, Masato Hoshi, Yasuko Yamamoto, Sanford P. Markey, and Kuniaki Saito
  • Organizer: 14th International Society for Tryptophan Research
  • Place of Presentation: Grand Rapids, USA
  • Year and Date: 2015-09-16
  • Int'l Joint Research
• [Presentation] Blockade of Indoleamine 2,3-dioxygenase reduces mortality from peritonitis and sepsis in mice by regulating function of CD11b+ peritoneal cells (2015)
  • Author(s): Masato Hoshi, Yosuke Osawa, Hiroyasu Ito, Mituru Seishima, Kuniaki Saito
  • Organizer: 14th International Society for Tryptophan Research
  • Place of Presentation: Grand Rapids, USA
  • Year and Date: 2015-09-16
  • Int'l Joint Research
• [Remarks] 論文１
  • URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556390/
• [Remarks] 論文２
  • URL: http://www.sciencedirect.com/science/article/pii/S0304394015001767