2002 Fiscal Year Final Research Report Summary
An analysis for mechanism of antitumor effects of dendritic cells treated with αGalactosylceramide
| Project/Area Number |
13672079
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 |
HASHIMOTO Wataru Dental Hospital, Assistant Professor, 歯学部附属病院, 助手 (30323033)
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| Project Period (FY) |
2001 – 2002
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| Keywords | galactosylceramide / antitumor effects / NKT cells / IFN-γ / IL-12 / dendritic cells / Intratumoral injection / tumor immunotherapy |
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| Research Abstract |
We have already reported that intratumoral injection of dendritic cells (DCs) treated with αGalactosylceramide (αGalCer) selectively activated natural killer T cells (NKT cells), resulting in regression of day 7 established poorly immunogenic tumors.
To clarify a role of IL-12 produced by DCs, α-GalCer treated-DCs harvested from IL-12 deficient mice can inhibits MCA205 tumor growth as strong as using WT's DCs. Interestingly, α-GalCer injection can not enhance the in vitro cytotoxicity of lymphocytes harvested from IFN-γ-deficient mice. Furthermore, the antitumor activity of using DCs treated with α-GalCer in IFN-γ-deficient mice is impaired comopletely. These results indicate that IFN-γ, but IL-12, plays critical role in these antitumor response of α-GalCer treated-DCs.
Next, we investigated the antitumor effects of αGalCer on human peripheral blood mononuclear cells (PBMC). Phenotypic analysis revealed an expansion of CD3+ CD161+ CD56- Vα24TCR+ T cells on PBMC. These results are consistent with the previous reports showing that α-GalCer selectively activates Vα14NKT cells in mice, suggesting that intratumoral injection of α-GalCer treated-DC should be considered a viable strategy for the generation of antitumor responses on human and for further clinical applications for head and neck tumors.
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