Analysis of the mechanisms for transient expression of HTLV-1 Tax and development of novel immunotherapy
| Project/Area Number |
17K07166
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | HTLV-1 / 癌 |
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| Outline of Final Research Achievements |
It was found that both transient expression of Tax and continuous expression of HBZ are important for the maintenance of ATL cell lines, such as MT-1 and KK-1. This finding was published PNAS (Mahgoub M, Yasunaga JI, Iwami S, Nakaoka S, Koizumi Y, Shimura K, and Matsuoka M. Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells. Proc Natl Acad Sci USA, 2018. doi: 10.1073/pnas.1715724115). ATAC-seq and ChIP-seq were carried out to see the effect of the transient expression of Tax on the epigenetic status of host cells. Analysis using HBZ transgenic mice showed that IL-10 plays important roles in T-cell proliferation induced by HBZ.
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| Academic Significance and Societal Importance of the Research Achievements |
Taxは強力ながん蛋白質であるが、免疫原性が高いためATL細胞では発現が抑制されており、発がんにおける意義は不明であった。本研究により、Taxの一過性発現とHBZの持続発現の発がんにおける意義を初めて報告した。本研究で得られた知見はHTLV-1の潜伏機構、発がん機構の解明に寄与できると考える。本研究で行ったTaxの発現誘導とTaxワクチンの併用療法の開発をさらに推進することで、ATLの発症予防法、再発予防法の開発に繋がると考える。
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Report
(4 results)
Research Products
(61 results)
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[Journal Article] IL-7R-Dependent Phosphatidylinositol 3-Kinase Competes with the STAT5 Signal to Modulate T Cell Development and Homeostasis.2020
Author(s)
Cui G, Shimba A, Ma G, Takahara K, Tani-Ichi S, Zhu Y, Asahi T, Abe A, Miyachi H, Kitano S, Hara T, Yasunaga JI, Suwanai H, Yamada H, Matsuoka M, Ueki K, Yoshikai Y, Ikuta K.
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Journal Title
The Journal of Immunology
Volume: 204
Issue: 4
Pages: 844-857
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Distinct gene expression signatures induced by viral transactivators of different HTLV-1 subgroups that confer a different risk of HAM/TSP.2018
Author(s)
Naito T, Yasunaga JI, Mitobe Y, Shirai K, Sejima H, Ushirogawa H, Tanaka Y, Nakamura T, Hanada K, Fujii M, Matsuoka M, Saito M.
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Journal Title
Retrovirology
Volume: 15
Issue: 1
Pages: 72-72
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] Tax-targeting dendritic cell therapy for ATL: A Phase Ia/Ib clinical study2018
Author(s)
Shiratsuchi, M., Fukuda, T., Iino, T., Hasegawa, A., Yasunaga, JI., Watanabe, K., Hirata, A., Utsunomiya, H., Ohno, H., Ishida, T., Akashi, K., Matsuoka, M., Kannagi, M. and Suehrio, Y.
Organizer
The 60th American Society of Hematology Annual Meeting and Exposition
Related Report
Int'l Joint Research
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[Presentation] HTLV-1 Infection in Multiple Lineages of Hematopoietic Cells.2017
Author(s)
Furuta, R.,Yasunaga, JI., Miura, M., Sugata, K., Saito, A., Akari, H., Ueno, T., Takenouchi, N., Fujisawa, J., Kouh, K., Shimizu, M., Matsuda, F., Melamed, A., Bangham, CR., and Matsuoka, M
Organizer
18th Interbational Conference on Human Retrovirology HTLV and Related Viruses
Related Report
Int'l Joint Research
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[Presentation] HBZ downregulates miR-455, a tumor suppressor microRNA in ATL2017
Author(s)
Ma, G., Yasunaga, JI., Miura, M., Matsumoto, T., Matsuoka, M
Organizer
第4回日本HTLV-1学会学術集会
Related Report
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