Regulation of the tumor malignant potentials and immune evasion by CD70-positive stromal cells.
Project/Area Number |
20K07410
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 49020:Human pathology-related
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Research Institution | Nagoya City University |
Principal Investigator |
Inaguma Shingo 名古屋市立大学, 医薬学総合研究院(医学), 教授 (80410786)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | CD70 / Cancer stroma / 大腸癌 / 癌間質細胞 / 癌間質 |
Outline of Research at the Start |
本研究は、ヒト大腸癌腫瘍組織内の間質成分に着目し、癌関連線維芽細胞(cancer-associated fibroblast, CAF)の性状を病理組織学的に解析するとともに、T細胞の活性化、分化を制御するCD70-CD27シグナル経路、特にCAFに異常発現するCD70に着目し、CD70陽性CAFによる大腸癌細胞の悪性形質制御、Th17やTregを介した免疫逃避の可能性を分子生物学的・臨床病理学的に解析することを目的としている。さらには、抗CD70抗体による腫瘍免疫療法の可能性を検討することで、新規腫瘍免疫療法を立案する基礎データを提供しうるものである。
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Outline of Final Research Achievements |
In the present study, the researchers established colorectal cancer (CRC) tissue arrays containing 270 CRC cases. Immunohistochemical analyses using tumor tissue arrays identified the prognostic significance of PBK, PHH3, SPATA18, and p53expressions in CRC cells. Furthermore, the significance of the CD47 expression in tumor-associated macrophage and periostin expression in colorectal cancer-associated fibroblasts were identified. In vitro studies identified the communication between cancer cells and periostin-positive fibroblasts. In pleural mesothelioma, patients with CD70- and PD-L1-positive tumors showed the worst clinical outcome. In vitro experiments identified that CD70 and PD-L1 cooperatively accelerated the migration and invasion of mesothelioma cells.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、腫瘍細胞、腫瘍間質双方に着目し、大腸癌細胞におけるPBK、ヒストンH3、またミトコンドリアのquality controlを行うといわれているSPATA18発現の臨床病理学的重要性とともに、p53発現症例が化学療法に対する反応性が良い可能性も明らかにした。腫瘍間質成分に関しては、マクロファージチェックポイント分子CD47の重要性や、大腸癌間質細胞に発現するperiostinの重要性も明らかにした。一方で、胸膜中皮腫細胞におけるCD70発現は、PD-L1と協調してその浸潤・遊走能、細胞増殖能、免疫逃避を制御するも明らかにした。今後、これらの分子を標的とした新規治療法の確立が望まれる。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Stromal POSTN Enhances Motility of Both Cancer and Stromal Cells and Predicts Poor Survival in Colorectal Cancer.2023
Author(s)
Ueki A, Komura M, Koshino A, Wang C, Nagao K, Homochi M, Tsukada Y, Ebi M, Ogasawara N, Tsuzuki T, Kasai K, Kasugai K, Takahashi S, Inaguma S.
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Journal Title
Cancers (Basel).
Volume: 15(3)
Issue: 3
Pages: 606-606
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] CD70 and PD-L1 (CD274) co-expression predicts poor clinical outcomes in patients with pleural mesothelioma.2023
Author(s)
Inaguma S, Ueki A, Lasota J, Komura M, Sheema AN, Czapiewski P, Langfort R, Rys J, Szpor J, Waloszczyk P, Okon; K, Biernat W, Schrump DS, Hassan R, Miettinen M, Takahashi S.
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Journal Title
J Pathol Clin Res.
Volume: 9(3)
Issue: 3
Pages: 195-207
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] SPATA18 expression predicts favorable clinical outcome in colorectal cancer.2022
Author(s)
Sugimura-Nagata, A., Koshino, A., Nagao, K., Nagano, A., Komura, M., Ueki, A., Ebi, M., Ogasawara, N., Tsuzuki, T., Kasai, K., Takahashi, S., Kasugai, K., Inaguma, S.
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Journal Title
International Journal of Molecular Science
Volume: 23
Issue: 5
Pages: 2753-2753
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The complete loss of p53 expression uniquely predicts worse prognosis in colorectal cancer.2022
Author(s)
Nagao, K., Koshino, A., Sugimura-Nagata, A., Nagano, A., Komura, M., Ueki, A., Ebi, M., Ogasawara, N., Tsuzuki, T., Kasai, K., Takahashi, S., Kasugai, K., Inaguma, S.
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Journal Title
International Journal of Molecular Science
Volume: 23
Issue: 6
Pages: 3252-3252
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Expression and Prognostic Significance of CD47-SIRPA Macrophage Checkpoint Molecules in Colorectal Cancer2021
Author(s)
Sugimura-Nagata A, Koshino A, Inoue S, Matsuo-Nagano A, Komura M, Riku M, Ito H, Inoko A, Murakami H, Ebi M, Ogasawara N, Tsuzuki T, Takahashi S, Kasugai K, Kasai K, Inaguma S
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Journal Title
International Journal of Molecular Science
Volume: 22
Issue: 5
Pages: 2690-2690
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] PBK expression predicts favorable survival in colorectal cancer patients2021
Author(s)
Nagano-Matsuo A, Inoue S, Koshino A, Ota A, Nakao K, Komura M, Kato H, Naiki-Ito A, Watanabe K, Nagayasu Y, Hosokawa Y, Takiguchi S, Kasugai K, Kasai K, Inaguma S, Takahashi S
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Journal Title
Virchows Archiv
Volume: -
Issue: 2
Pages: 277-284
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] High phospho-histone H3 expression uniquely predicts favorable survival among four markers of cellular proliferation in colorectal cancer.2021
Author(s)
Koshino A, Inoue S, Sugimura-Nagata A, Nishiyama T, Murakami H, Ito H, Riku M, Inoko A, Ebi M, Ogasawara N, Tsuzuki T, Kasugai K, Kasai K, Inaguma S.
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Journal Title
Pathol Int.
Volume: -
Issue: 5
Pages: 2690-2690
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Colorectal Adenocarcinomas Harboring ALK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 12 Cases and Review of the Literature.2021
Author(s)
Lasota J, Inaguma S, Izycka-Swieszewska E, Kaczorowski M, Kolos M, Kopczynski J, Michal M, Milione M, Okon K, Peksa R, Pyzlak M, Rys J, Waloszczyk P, Wejman J, Miettinen M.
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Journal Title
Am J Surg Pathol.
Volume: 44(9)
Issue: 9
Pages: 1224-1234
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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