| Project/Area Number |
14570195
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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 |
Experimental pathology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
IKEDA Hideyuki Sapporo Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (40301494)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Noriyuki Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (50158937)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Glioblastoma / CIITA / Class II / Histone acetylation / Squamotis cell carcinoma / Glioma / T細胞抗原 |
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| Research Abstract |
Class-II-restricted T-cell defined antigens are thought to be quite important for tumor immunology ; however, they are far less frequently identified than those of class-I-restricted antigens, chiefly because of its complex antigen presentation pathways. In order to enlarge the possibility for immunotherapy against glioblastoma, we have extensively studied the underlying mechanisms for class II expression in terms of its master regulator, class II transactivator(CIITA).
1.Facs analysis, first of all, demonstrated 3 subtypes of glioblastoma in terms of class II expression in the presence or absence of IFN-γ treatment.
2.Eight out of 12 glioblastoma cell lines(type2) upregulated class II molecules after IFN-γtreatment. This was mediated by activation of promoter III and IV of CIITA assessed by RT-PCR.
3.Normal human astrocyte cell line as well as surgically-removed glioblastoma specimens(9/11) revealed that the type2 glioblastoma represented typical phenotype of class II molecules.
4.Two of 12 glioblastoma cell lines(type1) constitutively expressed class II molecules without IFN-γ. This was mediated by transcriptional activation through wide area of histone acetylation spanning over 6kb in the promoter and enhancer region of CIITA.
We have extended the similar experimental approaches to other types of cancers such as head and neck squamous cell carcinoma, leukemia, and gastrointestinal carcinoma. Glioblastoma has proved to be specialized for class II expression. Thus, glioblastoma, stably transfected with CIITA may serve as antigen presenting cells and stimulate CD4-positive T-cells, which are particularly useful to identify glioblastoma specific antigens.
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