| Project/Area Number |
13470428
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
TAKAHASHI Yuzo Tokyo Medical and Dental University, Graduate School, Associate Professor, 大学院・医歯学総合研究科, 助教授 (50014329)
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| Co-Investigator(Kenkyū-buntansha) |
MARUOKA Yutaka Tokyo Medical and Dental University, Graduate School, Associate Professor, 大学院・医歯学総合研究科, 助手 (10323726)
AZUMA Miyuki Tokyo Medical and Dental University, Graduate School, Professor, 大学院・医歯学総合研究科, 教授 (90255654)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥9,800,000 (Direct Cost: ¥9,800,000)
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| Keywords | Antitumor immunity / Dendritic cell / Sentinel lymph nodes / Costimulatory molecule / 口腔癌 / 腫瘍免疫 |
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| Research Abstract |
B7-H1 is one of ligands for an immunoregulatory molecule, PD-1. Our studies using a murine oral squamous cell carcinoma cell line, NRS1 revealed that the endogenously induced B7-H1 on NRS1 cells regulated negatively anti-tumor immune responses through PD-1. In contrast, the B7-H1. expressed at H1gh levels by gene transduction enhanced the antitumor responses in a PD-1-independent manner. These results suggest that B7-H1-mediated immune regulation seems to be very complicated.
On one hand, B7-H1 is also induced on dendritic cells (DC) with B7-DC, wH1ch is another ligand for PD-1. Unlike B7-H1, B7-DC is selectively induced on DC. In the draining lymph nodes after the hapten sensitization, CD86^<high> DC co-expressed B7-DC witH1n the migrating CD11b^+CD11c^+ DC from the skin. The semi-mature DC, wH1ch expressed low levels of CD86 expressed B7-H1 but not B7-DC. The administration of anti-B7-H1 or anti-PD-1 monoclonal antibody at the hapten-sensitization enhanced the responses to the hapten-challenge. These results suggest that the PD-1:B7-H1 pathway is involved in tolerance induction.
The inoculation of H1ghly metastatic NRS1 cells into the tongue induced a rapid expansion of CD11b^<++> large cells in the draining LN. These cells expressed low CD86 and B7-H1 and seem to induce tolerance in the sentinel LN. Our results suggest the possibility that the migrated DC in the sentinel LN caused tolerance induction, wH1ch is dependent upon B7-H1.
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