2020 Fiscal Year Final Research Report
Endocrine-related adverse events induced by immune checkpoint inhibitors: from clinical features to mechanistic insights
| Project/Area Number |
19K23942
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0902:General internal medicine and related fields
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2019-08-30 – 2021-03-31
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| Keywords | 免疫チェックポイント阻害薬 / PD-1 / 甲状腺 / 下垂体 / 自己抗体 / irAE / ニボルマブ |
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| Outline of Final Research Achievements |
We conducted a clinical study using real-world data of Kyoto University Hospital. This study revealed distinct clinical features of immune-related adverse events invloving the pituitary gland (pituitary irAEs) induced by anti-PD-1 antibody. Pituitary irAEs by PD-1 blockade are dissimilar to those by CTLA-4 blockade: the most impressive point is the concomitant thyroid dysfunction (Clin Endocrinol(Oxf). 2021).
On the other hand, we set a hypothesis "Autoantibodies recognizing antigens common to the thyroid gland and cancers are produced in thyroid irAEs," suggested by the clinical finding that thyroid irAE is a prognostic factor. We performed co-immunoprecipitation assay using sera from patients with thyroid irAEs and found novel autoantibodies (bioRxiv. 2021).
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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薬の使用症例の増加に伴い、特有の有害事象（irAE）の中でも10%以上の高い頻度で生じる内分泌障害のマネジメントは不可欠である。最も普及し多くの症例に使われている抗PD-1抗体について臨床研究を行い、これまで報告してきた甲状腺irAEだけでなく、下垂体irAEについても臨床像を明らかにした。さらには発症機序として、新規自己抗体が関与する可能性を示すデータを得た。
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