Novel treatment strategy to focus on efficient antigen presentation by HLA class I molecules in head and neck carcinoma.
| Project/Area Number |
16591695
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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 | Asahikawa Medical College |
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Principal Investigator |
OGINO Takeshi Asahikawa Medical College, School of Medicine, assstant, 医学部, 助手 (00312455)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | HLA class I antigen / head and neck cancer / antigen presentation / antigen processing / immunoescape mechanism |
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| Research Abstract |
we examined formalin fixed, paraffin embedded tissues of 63 laryngeal carcinoma, 36 nasopharyngeal carcinoma, 34 oropharyngeal carcinoma and 45 hypopharyngeal carcinoma using immunohistochemistry to assess HLA class I antigen and antigen processing machinery (APM) component expression in the lesions. HLA class I antigen expression was downregulated in at least 80% of each lesion. LMP2,TAP1 and tapasin were downregulated in at least 70% lesion of laryngeal and nasopharyngeal carcinomas. Although HLA class I antigen downregulation was associated with unfavorable clinical course of the disease in laryngeal and nasopharyngeal carcinomas, it was not associated in oropharyngeal and hypopharyngeal carcinomas.
IFN-γ upregulated not only HLA class I antigen expression but also LMP2,TAP1 and tapasin expression. In addition, expression level of LMP2,TAP1 and tapasin were associated with that of HLA class I antigen. Lack of recognition of head and neck squamous cell carcinoma cells by CTL was associated with marked downregulation of LMP2,TAP1,TAP2 and tapasin and was restored by incubation with IFN-γ and by transfection with TAP1 cDNA.
These results suggested that abnormalities of HLA class I antigen and APM components may be an immunoescape mechanism in head and neck squamous cell carcinomas. HLA class I antigen expression and recognition by CTL were corrected by restoration of the abnormalities of APM by transfection of APM components and by IFN-γ. As a result, carcinoma cells are easily eliminated by host immune system.
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Report
(3 results)
Research Products
(11 results)
