2023 Fiscal Year Final Research Report
IL-18-induced type I immune response and regulation of immune checkpoints by tumor neoantigens
| Project/Area Number |
21K07229
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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 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Hyogo Medical University (2022-2023)
Hyogo University of Health Sciences (2021) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大野 喜也 兵庫医科大学, 薬学部, 准教授 (40509155)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 癌免疫治療 / IL-18 / 免疫チェックポイント / I型免疫応答 / 腫瘍ネオ抗原 / 免疫関連有害事象 / 併用薬 |
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| Outline of Final Research Achievements |
Through research aimed at enhancing the therapeutic effects of immune checkpoint inhibitors and overcoming treatment resistance, the following results were obtained: 1) IL-18 enhances the therapeutic effects of immune checkpoint inhibitors by acting on both NK cells and dendritic cells, promoting their crosstalk involving XCL1 and IL-12.
2) A dual deficiency of MLH1, a key molecule in DNA repair, and PD-L1 may confer increased sensitivity to immune checkpoint therapy.
3) A retrospective observational study was conducted to elucidate the effects of concomitant drug use in clinical practice on immune checkpoint therapy of patients with lung cancer.
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| Free Research Field |
免疫学
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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は担癌宿主のT細胞を抑制状態から解放し、強い抗腫瘍効果を発揮する。
しかし、半数以上の患者には未だ十分な腫瘍縮小効果が見られない。また、克服すべき副作用として免疫関連有害事象が残されている。現在、免疫チェックポイント阻害薬の抗腫瘍効果を増強し、治療抵抗性を克服する新しい戦略の開発が強く望まれている。IL-18による免疫チェックポイント阻害薬の抗腫瘍効果の増強機構やDNA修復阻害による癌細胞の異物性の増大並びに併用薬が免疫チェックポイント阻害治療に及ぼす影響の解明は、臨床医学的に大きな意義を持つ。
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