Interleukin-18 activates Natural Killer cells and induces tumor apoptosis ; clinical applications for head and neck tumors.
| Project/Area Number |
14370655
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Tohoku University |
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Principal Investigator |
ECHIGO Seishi Tohoku University, Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (70005114)
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| Co-Investigator(Kenkyū-buntansha) |
MORIKAWA Hidehiro Tohoku university, Graduate School of Dentistry, Assistant Professor, 大学院・歯学研究科, 助手 (60302155)
HASHIMOTO Wataru Tohoku University, Hospital, Assistant Professor, 病院・助手 (30323033)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥11,500,000 (Direct Cost: ¥11,500,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2003: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | IL-18 / antitumor / natural killer cells / IFN-γ / apoptosis / dendriticcells / innate immunity / specific immunity |
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| Research Abstract |
We have investigated the antitumor effects of IL-18 in marine and human models and reported that IL-18 activated natural killer cells and induced tumor apoptosis. Moreover, tumor apoptosis induced tumor specific cytotoxic T lymphocytes (CTL) by using dendritic cells.
We investigated the antitumor effects of combining IL-18 and IL-2 on human peripheral blood mononuclear cells. The combination of these two cytokines produced a large amount of IFN-γ and enhanced tumor cell death against tumor cell lines. Moreover, phenotypic analysis revealed an expansion of CD56+ CD161+ CD3-NK cells on PBMC.
In this project, we investigated the antitumor effects of IL-18 in human model in detail. We revealed that co-culture with tumor cells and PBMC activated by IL-2 and IL-18 induced tumor apoptosis on human squamous cell carcinoma cell line. Next, we examined the expression of TRAIL and FasL on IL-18-stimulated PBMC by using RT PCR and revealed that TRAIL and FasL mRNA were upregulated by IL-18 stimulation. These results suggest that TRAIL and FasL play critical role for IL-18-induced tumor apoptosis.
Next, we analyzed a response to IL-18 on PBMC from oral cancer patient. We collected patients' PBMC before and after chemotherapy, and investigated changes of NK or T cells. In this study, we have applied to committee of Tohoku University Hospital for the clinical application and were permitted. Then, we have started to collect clinical samples and got some samples. But we cannot analyze data because sample numbers were not so much. We hope that we will continue collecting samples from cancer patients and develop cancer immunotherapy by using IL-18.
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Report
(4 results)
Research Products
(19 results)
