2019 Fiscal Year Final Research Report
Clinical validation of microenvironmental control related to malignant trait acquisition of triple negative breast cancer
| Project/Area Number |
17K10559
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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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| Research Field |
General surgery
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| Research Institution | Osaka City University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
藤田 寿一 大阪市立大学, 大学院看護学研究科, 准教授 (30212187)
高島 勉 大阪市立大学, 大学院医学研究科, 講師 (80336776)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | トリプルネガティブ乳癌 / 腫瘍微小環境 / 腫瘍免疫 / Precision medicine |
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| Outline of Final Research Achievements |
It has been clarified that the evaluation of host tumor microenvironment (TME) plays an important role in predicting prognosis and therapeutic effect in cancer treatment. The applicant examined the dynamic changes of TME from the viewpoints of epithelial-mesenchymal transition (EMT), tumor hypoxia, cancer metabolism competition and tumor immune response, and clarified the factors, plasticity and heterogeneity related to the changes. In this study, we evaluated tumor-infiltrating lymphocytes (TILs) for dynamic changes in TIME due to modification of drug therapy and metastasis/recurrence, and revealed that the CD8/FOXP3 ratio is a useful marker. We also developed a new evaluation index called RCB-TILs that combines TILs with Residual Cancer Burden (RCB), which is a residual tumor after neoadjuvant chemotherapy.
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| Free Research Field |
乳癌
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| Academic Significance and Societal Importance of the Research Achievements |
申請者らは，本研究のテーマである『TNBCの悪性形質獲得に関わる微小環境制御の臨床的検証』についてEMTや腫瘍免疫，内分泌感受性の側面から探究をすすめ，国内外に発信した．そして実臨床への応用可能なTNBCの新たな治療戦略の構築を目的とした基礎研究・臨床研究を推進している．薬物療法前後や原発巣/転移巣の標本を使用するなど癌微小環境を動的に捉え，これらに変化を及ぼす癌間質の関与や腫瘍免疫の誘導などを検証した．本研究により癌微小環境は動的な変化を示し，その分子機構にEMTや免疫環境が関与していることを明らかにした．
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