Analysis of biological factors involved in tumor immunity and its application to personalized radiotherapy.
| Project/Area Number |
20K16764
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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 52040:Radiological sciences-related
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 腫瘍免疫 / リキッドバイオプシー / 放射線治療 / 治療効果予測 |
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| Outline of Research at the Start |
本研究では腫瘍免疫関連タンパクの発現と放射線治療成績の相関を解明し、臨床応用に結びつけることを目的とする。
具体的には、(A) 治療開始前の生検検体および術後摘出標本を用いた、腫瘍免疫関連タンパクの免疫組織染色による放射線治療効果予測、(B) 血中のPD-L1(Programmed death ligand-1)測定による腫瘍免疫応答の解析、(C)腫瘍免疫の制御に関わる血中マイクロRNAの同定を行い、癌細胞の腫瘍免疫関連タンパクを用いた放射線感受性予測法の臨床応用と個別化放射線治療の実用化を目指す。
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| Outline of Final Research Achievements |
We investigated the expression of miRNAs in exosomes and tumor-infiltrating CD8-positive and FoxP3-positive T cells in blood before treatment in patients with uterine cervical cancer treated with definitive radiotherapy. The results and their prognostic relevance were also investigated. As a result, we identified nine miRNA signatures that were differentially expressed with or without recurrence. The expression of some miRNA signatures was inversely correlated with the number of tumor-infiltrating CD8-positive and FoxP3-positive T cells, suggesting a possible association between tumor immunosuppression and suppression of chemoradiotherapy efficacy.
These results indicate that the use of miRNA signatures may improve noninvasive monitoring and personalized treatment of cervical cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、腫瘍免疫機構が解明されつつあり、臨床においても免疫チェックポイント阻害薬が承認され効果が認められている。しかし、放射線治療と腫瘍免疫機構の関連については未解明の部分が多い。この研究では子宮頸癌における腫瘍免疫関連タンパクの発現や腫瘍免疫の制御に関わる血中マイクロRNAと放射線治療の成績について比較検討を行っている。その結果、いくつかのmiRNAシグネチャの発現は腫瘍免疫との関連を示すとともに化学放射線治療の効果にも影響を及ぼしている可能性が示された。
これにより腫瘍免疫やmiRNAに基づいた個別化治療を行うことで、化学放射線治療の効果を高められる可能性がある。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Predictive value of an exosomal microRNA-based signature for tumor immunity in cervical cancer patients treated with chemoradiotherapy.2023
Author(s)
Someya M, Hasegawa T, Tsuchiya T, Kitagawa M, Fukushima Y, Gocho T, Mafune S, Ikeuchi Y, Kozuka Y, Idogawa M, Hirohashi Y, Torigoe T, Iwasaki M, Matsuura M, Saito T, Sakata KI.
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Journal Title
Med Mol Morphol.
Volume: 56(1)
Issue: 1
Pages: 38-45
DOI
Related Report
Peer Reviewed
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[Journal Article] Combined chemoradiotherapy and programmed cell death-ligand 1 blockade leads to changes in the circulating T-cell receptor repertoire of patients with non-small-cell lung cancer.2022
Author(s)
Someya M, Tokita S, Kanaseki T, Kitagawa M, Hasegawa T, Tsuchiya T, Fukushima Y, Gocho T, Kozuka Y, Mafune S, Ikeuchi Y, Takahashi M, Moniwa K, Matsuo K, Hasegawa T, Torigoe T, Sakata KI.
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Journal Title
Cancer Sci.
Volume: 113(12)
Issue: 12
Pages: 4394-4400
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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