2018 Fiscal Year Final Research Report
Research for the pathogenesis of hypophysitis induced by immune checkpoint inhibitors
| Project/Area Number |
16K19552
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Endocrinology
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| Research Institution | Nagoya University |
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Principal Investigator |
Iwama Shintaro 名古屋大学, 医学部附属病院, 病院講師 (00733536)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 免疫関連有害事象 / 抗PD-1抗体 / 抗CTLA-4抗体 / 甲状腺炎 |
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| Outline of Final Research Achievements |
In this study, we tried to make a novel mouse model for hypophysitis which is one of immune related adverse events (irAEs) induced by immune checkpoint inhibitors through the repeated injection with anti-CTLA-4 antibody or anti-PD-1 antibody. We also tried to make a mouse model for thyroiditis as another irAEs model. Finally, we established a novel mouse model which developed destructive thyroiditis after the administration of anti-PD-1 antibody. Using this model, we clarified the cells expressing PD-1 and PD-L1 in the inflamed thyroid glands.
These findings lead to clarify not only the pathogenesis of irAEs induced by immune checkpoint inhibitors but also the mechanisms of autoimmune diseases in endocrine organs.
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| Free Research Field |
内分泌学
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| Academic Significance and Societal Importance of the Research Achievements |
免疫チェックポイント阻害剤（抗CTLA-4抗体や抗PD-1抗体）は、進行悪性腫瘍で有効性が報告されているが、一方で下垂体炎を含む免疫関連副作用（irAEs）が発症することが問題となっている。内分泌関連の副作用として下垂体炎と甲状腺炎の頻度が高い。
本研究では、内分泌irAEsとして下垂体炎および甲状腺炎のマウスモデルの開発に取り組んだ。その結果、抗PD-1抗体により甲状腺炎を発症する新たなマウスモデルの開発に成功し、甲状腺炎組織におけるPD-1およびPD-L1を発現する細胞を解明した。甲状腺irAEsの発症機序の解明は、他のirAEsおよび自己免疫疾患の病態解明につながる可能性が期待できる。
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