| Project/Area Number |
21K16224
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | Shinshu University |
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Principal Investigator |
Nakamura Kenta 信州大学, 学術研究院医学系, 助教 (90804170)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 悪性黒色腫 / 術後補助療法 / レパトア / ケモカイン |
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| Outline of Research at the Start |
悪性黒色腫は術後補助療法（抗PD-1抗体）を行っても、術後12か月以内に約3割の再発がみられることから、この再発抑制のメカニズムを解析し、再発抑制による予後改善につなげるために、術後補助療法前後での末梢血のT細胞クローンやサイトカインやケモカインの変動やが再発抑制と関連するのか解析を行う。
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| Outline of Final Research Achievements |
In the cases in which recurrence occurred with adjuvant therapy (9 cases), T-cell clonal proliferation decreased after treatment, while in the cases in which recurrence did not occur (6 cases), T-cell clonal proliferation significantly increased after treatment. The T-cell clones that increased in this peripheral blood were the same as the T-cell clones infiltrating the resected tumor specimen, and were considered to be clones that recognized the tumor. In addition, the patients who did not experience recurrence had T-cell clonal proliferation comparable to that seen in six patients with advanced-stage malignant melanoma whose tumors had shrunk for more than two years with anti-PD-1 antibody therapy, suggesting that this clonal proliferation may have played a role in the prevention of recurrence.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性黒色腫の術後再発が予後不良の原因となっており、2018年より術後補助療法（術後12か月間の免疫チェックポイント阻害薬（抗PD-1抗体））が開始された。これにより、術後12か月間に約4割あった再発が約3割に減少した。今回、さらなる再発リスクの軽減のため、再発を予測する因子を解析したところ、治療開始後の末梢血のT細胞クローンの増殖がみられないことが再発群で有意に示された。このような症例群では、再発のリスクが高いと考え、画像検査などを頻回に行うなど早期発見が必要である。また、今後、T細胞クローンの増殖を促す治療との併用などが期待される。
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