| Project/Area Number |
17K15006
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor diagnostics
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 乳癌 / 腫瘍免疫 / T細胞 / 免疫バイオマーカー / 癌 |
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| Outline of Final Research Achievements |
We evaluated the expression pattern of CD8 and PD-L1 for triple negative breast cancer using the tissue material before and after chemotherapy. Breast tumor was categorized into 4 subtypes according to the expression pattern. Patients with Inflamed/PD-L1neg tumor had better prognosis compared with patients with Inflamed/PD-L1pos tumor (P=0.0365). There was no survival difference in patients with between Excluded and Immune desert (P=0.371).
We performed comprehensive analyses of T cell receptor (TCR) by using TCR DNA sequencing. Diversity index was also calculated for HER2 positive or triple negative breast cancer at the blood sample which was obtained before and after anthracycline based chemotherapy. As a result, the diversity index could be predictive for the efficacy of chemotherapy in HER2 positive or triple negative breast cancer. The some unique clones might be also predictive for the efficacy of chemotherapy.
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| Academic Significance and Societal Importance of the Research Achievements |
現在の乳癌薬物療法において最も問題となっているのは、追加治療の必要な患者群と追加治療が不要もしくは現治療が過剰である患者群の層別化が不十分であることである。本研究では、術前治療による遺残腫瘍症例における免疫バイオマーカーを検討し今後免疫チェックポイント阻害剤での追加治療が必要な症例を抽出することに成功した。これにより高価な分子標的治療の適応となる症例群が明確となった。また、T細胞レパトア解析では乳癌症例では過去に無いデータを創出した。今後これらのデータがもととなり、腫瘍抗原に反応する特異的なTCRであったり、必要な多様性の程度が明らかになってくると思われる。
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