2017 Fiscal Year Research-status Report
The development of the efficacious anti-tumor DC therapies using TGF-beta antagonists
| Project/Area Number |
17K15735
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
尹 晶煥 東京医科大学, 医学部, 兼任助教 (30748885)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Keywords | dendritic cell / TGF-β / Smad |
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| Outline of Annual Research Achievements |
<Research Plan 2> Molecular mechanisms how TGF-β regulates differentiation and maturation of DC subsets: I have found that selective repression of SMAD3 directs conventional DC, whereas its maintenance directs plasmacytoid DC differentiation and clarified the molecular mechanisms. I have presented the results at the American Association for Cancer Research Annual Meeting 2017, Washington DC, USA, The 5th Annual Meeting of the International Cytokine and Interferon Society, Kanazawa, Japan and the 46th Annual Meeting of The Japanese Society for Immunology, Sendai, Japan. I have been awarded by 2016 Excellent Thesis Award (Outstanding Doctoral Research Award), University of Tsukuba, Japan and the Kishimoto Travel Awards at the 5th Annual Meeting of the International Cytokine and Interferon Society, Kanazawa, Japan in 2017.
<Research Plan 1> The mechanisms how systemic TGF-β antagonists exert dose-dependent divergent effects on tumor immunity: I have found that the treatment with high-dose activin receptor-like kinase5 inhibitor, EW7197 exacerbated the murine B16 melanoma model by rather accelerating the SMAD-mediated TGF-β signaling via blocking the negative feedback loop. I have found that dose-dependent anti-tumor and tumor-promoting effects of TGF-β antagonists are due to the distinct SMAD expression patterns in cell-specific manners.
<Research Plan 3> Optimization of DC-based anti-tumor immunotherapies using TGF-β antagonists: I have optimized the culture condition for adoptive DC therapy for the murine B16 melanoma model.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
I have submitted the paper on Research Plan 2, which is currently under revision. I am preparing the papers on Research Plan 1.
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| Strategy for Future Research Activity |
< Research Plan 1> I am preparing the manuscripts for submission.
<Research Plan 2> I am revising the paper.
<Research Plan 1 and 3> I will set up the 4T1 mammary carcinoma lung metastasis model.
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| Causes of Carryover |
The reagents planned to be purchased were more expensive than the remaining amount. I will purchase the reagents in the next fiscal year.
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[Presentation] Selection of Smad2 for TGF-β to suppress dendritic cells by STAT3/c-Ski-induced repression of Smad32017
Author(s)
Jeong-Hwan Yoon, Eunjin Bae, Katsuko Sudo, Seok Hee Park, Michael Weinstein, Susumu Nakae, Jin Soo Han,InKyu Lee, Ji Hyeon Ju, Takayuki Sumida, Masahiko Kuroda, Keiji Miyazawa, Mitsyasu Kato, Mizuko Mamura
Organizer
The American Association for Cancer Research Annual Meeting 2017, Washington DC, USA
Int'l Joint Research
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[Presentation] Repression of SMAD3 by STAT3 and c-Ski Is Essential for Conventional Dendritic Cell Differentiation2017
Author(s)
Jeong-Hwan Yoon, Eunjin Bae, Katsuko Sudo, Seok Hee Park, Michael Weinstein, Susumu Nakae, Jin Soo Han,InKyu Lee, Ji Hyeon Ju, Takayuki Sumida, Masahiko Kuroda, Keiji Miyazawa, Mitsyasu Kato, Mizuko Mamura
Organizer
The 5th Annual Meeting of the International Cytokine and Interferon Society, Kanazawa, Japan
Int'l Joint Research
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[Presentation] Repression of SMAD3 by STAT3 and c-Ski Is Essential for Conventional Dendritic Cell Differentiation2017
Author(s)
Jeong-Hwan Yoon, Eunjin Bae, Katsuko Sudo, Seok Hee Park, Michael Weinstein, Susumu Nakae, Jin Soo Han,InKyu Lee, Ji Hyeon Ju, Takayuki Sumida, Masahiko Kuroda, Keiji Miyazawa, Mitsyasu Kato, Mizuko Mamura
Organizer
The 46th Annual Meeting of The Japanese Society for Immunology, Sendai, Japan
