2006 Fiscal Year Final Research Report Summary
Antitumor effect of cell-mediated immunity for head and neck squamous cell carcinoma
| Project/Area Number |
16591707
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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 |
Otorhinolaryngology
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| Research Institution | Kobe University |
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Principal Investigator |
ISHIDA Haruhiko Kobe University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (70223005)
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| Co-Investigator(Kenkyū-buntansha) |
NIBU Ken-ichi Kobe University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (20251283)
OTSUKI Naoki Kobe University Hospital, Lecturer, 医学部附属病院, 講師 (40343264)
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| Project Period (FY) |
2004 – 2006
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| Keywords | B7-1(CD80) / KLN205 cell line / DBA / 2 mouse / antitumor effect / vaccine effect / CD8 / MHC Class I |
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| Research Abstract |
A murine squamous cell carcinoma cell line, KNL205, was infected with adenoviral vectors carrying either B7-1 (AdB7) or LacZ gene (AdCL). Infected cells were injected subcutaneously into the flank of DBA/2 mice. AdB7-infected cells grew significantly slower than AdCL-infected cells. Significant growth suppression of re-challenged non-infected parental cells was observed in the mice immunized with AdB7-infected cells but not in those immunized with AdCL-infected cells.
Immunohistochemical study was performed to analyze the production of CD80 (product of the B7-1 gene) and of MHC class I antigen, as well as the type of T lymphocytes in the tumor tissues. Positive staining for CD80 was detected in the majority of tumor cells in the AdB7-infected group, but only in occasional cells in the AdCL-infected or non-infected group. Staining for the MHC Class I antigen was observed in most of the tumor cells in all three groups. A large number of CD8-positive cells were seen in AdB7-infected tumors, while there were few in the other two groups. CD4-positive cells were rare in all three groups.
These results indicate that induced B7-1 gene expression provided AdB7-infected SCC cells with a function as APC (antigen presenting cell) such as dendritic cell. They then activated CD8-positive T lymphocytes by means of CD80 costimulation with MHC class I, resulting in the anti-tumor effect. Moreover, in the "vaccine experiment", an anti-tumor effect was attained in the mice immunized with AdB7-infected cells, suggesting that vaccination augments not only local but also systemic immune response. Further studies to achieve high-level and long-acting expression of B7-1 and to examine the synergistic effect of various cytokines may lead to the clinical application of B7-1 gene transfer as a new therapeutic alternative for head and neck cancers.
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