2023 Fiscal Year Final Research Report
Development of Innovative Immune Combination Therapy Based on Tumor and Stromal Morphology of Colorectal Cancer
| Project/Area Number |
22K16480
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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 55020:Digestive surgery-related
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| Research Institution | Gunma University |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Keywords | 上皮間葉転換 / 癌関連線維芽細胞 / 腫瘍免疫関連因子 / desmoplastic reaction / 低分化胞巣 / 大腸癌 |
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| Outline of Final Research Achievements |
We classified advanced colorectal cancer morphologically on histopathological specimens based on desmoplastic reaction (DR), which reflects the cancer function of related fibroblasts, and poorly differentiated clusters (PDCs), which are signs of dedifferentiation in advanced cancer areas. Moreover, we evaluated epithelial-to-mesenchymal transition (EMT) based on this classification, and colorectal cancer with EMT had a poor prognosis. In addition, we evaluated the fibrotic components within the tumor, and found that cases with many fibrotic components had a poor prognosis, and such cases were associated with a significant decrease in CD3+ and CD8+ cells. Furthermore, the local immune status of the tumor was evaluated, and the prognosis of cases in which tumor immunosuppression was observed was poor. We revealed that immature DR, associated with EMT, and severe intratumoral fibrosis were associated with decreased immune cell infiltration and worsened prognosis.
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| Free Research Field |
消化器外科学関連
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果からEMT誘導の引き起こされている腫瘍先進部のDRが未熟な症例や腫瘍内の線維化が強い症例は腫瘍免疫抑制と関連し、予後の悪化を引き起こしていることが明らかとなった。大腸癌の形態学的特徴や腫瘍免疫に関連する各種指標から予後不良症例を抽出し集学的治療を行うことで進行大腸癌の予後を向上させうる可能性や、EMT誘導を引き起こしている症例に対して免疫療法の感受性を高めることで予後を改善させうる新たな治療開発につながる基礎データを得ることができた点で学術的・社会的意義があると考える。
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