| Project/Area Number |
19K17153
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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 | Kurume University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 子宮頸癌 / 放射線治療 / 高線量率密封小線源治療 / PD-L1 / CD163 / 腫瘍微小環境 / 根治的放射線療法 / 腫瘍周囲組織 / 2年局所制御率 / 化学放射線療法 / 2年無増悪生存期間 / 低酸素 / PD-1 / CD8陽性T細胞 / 経時的変化 / CD-8陽性T細胞 |
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| Outline of Research at the Start |
子宮頸癌に対して化学放射線療法が確立されているが，中には治療不応例が存在し，腫瘍のPD-L1発現量の増加によりそのエフェクターであるCD8陽性T細胞が抑制されているか，あるいはCD8陽性T細胞が組織から欠如していると考えられる．このように，腫瘍制御においてはPD-L1発現量やCD8陽性T細胞数の動態を理解する必要がある．本研究は腫瘍の免疫回避機構の一つであるPD-1/PD-L1とCD8陽性細胞に着目し，化学放射線療法を行った子宮頸癌症例を対象に，その初期治療効果や予後と，腫瘍細胞のPD-L1発現量およびCD8陽性T細胞数の変化との関連性を調べる．
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| Outline of Final Research Achievements |
This study investigated changes in the immunity of the tumor microenvironment (TME) during standard radical RT for cervical cancer and determined whether these changes affect prognosis. Twenty-six patients who had completed radical RT for cervical cancer were categorized into the following two groups according to whether the cancer recurred and/or metastasized within 2 years after the start of treatment, and we assessed immunohistolical marker between two groups and assessed its effect on prognosis. The expression levels of PD-L1 and CD163 in the TME in the treatment success group were lower than those in the treatment failure group at the midpoint during brachytherapy, and the 2-year progression-free-survival (PFS) rate depended on the expression levels of PD-L1 and CD163. The expression rates of CD163 and PD-L1 in the TME during brachytherapy were related to treatment response and the 2-year PFS.
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| Academic Significance and Societal Importance of the Research Achievements |
子宮頸癌に対する根治的放射線療法において，腫瘍免疫抑制分子の一つであるPD-L1と，腫瘍増大に関わるM2マクロファージの代表マーカーであるCD163に注目した治療法の開発に貢献する結果となった．
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