2022 Fiscal Year Final Research Report
Proposing new treatment options for cutaneous lymphomas based on the comprehensive analysis of the pathogenesis of the diseases
| Project/Area Number |
20K08683
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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 53050:Dermatology-related
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 皮膚悪性リンパ腫 / Cyclophilin A / CD147 / IL-34 / PD-1 / 自己分泌因子 / 腫瘍微小環境 / 免疫チェックポイント分子 |
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| Outline of Final Research Achievements |
I revealed that tumor cells of cutaneous T-cell lymphoma (CTCL) produced Cyclophilin A (CypA) and expressed its receptor, CD147, on the cell surface and that CypA induced the proliferation of tumor cells through binding to CD147 in an autocrine manner. These results suggest that the disruption of CD147-CypA interactions could be a new therapeutic strategy for the treatment of CTCL.
I also found that tumor cells of Sezary syndrome expressed IL-34 and that serum IL-34 levels were increased in Sezary syndrome patients. Considering that IL-34 has the capacity to promote Th2 immune responses that help tumor progression, the suppression of IL-34 expression or function may be a new therapeutic option for Sezary syndrome.
I finally revealed that CTCL tumor cells coexpressed PD-1 and PD-L1, suggesting that the PD-1-PD-L1 interaction may affect the proliferation of tumor cells. Although further analysis is needed, these molecules can be a therapeutic target of CTCL.
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| Free Research Field |
皮膚悪性リンパ腫
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| Academic Significance and Societal Importance of the Research Achievements |
皮膚T細胞リンパ腫では、腫瘍細胞の種類や浸潤形態などで異なるが、多剤併用化学療法を含めた複数の治療に抵抗性があり、診断確定後数年以内に死亡するケースも少なくない。近年、このような進行例、難治例に対して、複数の新規薬剤が使用されるようになってきたが、造血幹細胞移植以外に長期コントロールを達成できる治療法は未だなく、新規治療法が切に求められている疾患である。本研究では、複数の新規治療戦略、治療標的を見出すことができ、将来的に難治性患者に新たな治療を提供する礎となるような発見ができたと考える。また、同様の機構が、他のT細胞リンパ腫で見られる可能性があり、新規研究にも繋がりうると考えられる。
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