2020 Fiscal Year Final Research Report
Investigation of activated innate immunity on anti-tumor effect: the effect of polymers on cellular uptake of apoptotic-cells induced by GPER-target drug
| Project/Area Number |
18K06008
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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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| Review Section |
Basic Section 42020:Veterinary medical science-related
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| Research Institution | Azabu University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | Gタンパク質結合エストロゲン受容体 / 膜型エストロゲン受容体 / イヌ肥満細胞腫 / アポトーシス / 遺伝子導入剤 / 樹状細胞 / 自然免疫活性化 |
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| Outline of Final Research Achievements |
Dendritic cells are typical antigen-presenting cells. It has recently been reported that dendritic cells phagocytose tumor cells and that tumor cell DNA activates DNA sensors inside dendritic cells. However, states of "antigen excess/antigen overload", when dendritic cells are persistently presented with excess amounts of tumor antigens, can induce T cell exhaustion, resulting in an inefficiently functioning acquired immune system; this makes it more difficult to eliminate tumors. In this study, we examined whether it might be possible to (1) induce tumor cell death efficiently without creating excess of antigens and (2) activate dendritic cells by ensuring a stable presence of tumor DNA in dendritic cells that have phagocytosed dead tumor cells.
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| Free Research Field |
獣医免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
ヒト腫瘍悪性度との関連性やこれまでの我々の知見から標的分子としてGPERに着目し、イヌ肥満細胞腫細胞においてGPERの発現が高いことを明らかにした。GPER標的薬をイヌ肥満細胞腫細胞に投与すると細胞死を誘導した。さらにCD117分子の発現が低下しているイヌ肥満細胞腫細胞でGPER発現が高いことを見出した。これはCD117発現低下によりCD117標的薬の効果が低いイヌ肥満細胞腫でのGPER標的薬の可能性を示唆する。一方、遺伝子導入用高分子材料による取り込みをマウス樹状細胞を用いて検討したが、核酸・タンパク質は取り込みを促進したが、死細胞の効率的な取り込みは現段階では認められず現在も検討中である。
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