Effects of hypoxic environment and HIF-1 on antitumor immune response of oral squamous cell carcinoma
| Project/Area Number |
23390430
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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 |
Pathobiological dentistry/Dental radiology
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| Research Institution | Kochi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
UDAKA Keiko 高知大学, 教育研究部医療学系, 教授 (40263066)
YAMADA Tomohiro 九州大学, 歯学研究科(研究院), 准教授 (60335619)
SASABE Eri 高知大学, 教育研究部医療学系, 助教 (40363288)
KITAMURA Naoya 高知大学, 教育研究部医療学系, 助教 (70351921)
RI Yasuhiro 高知大学, 医学部附属病院, 医員 (70587526)
OHNO Seiji 高知大学, 教育研究部医療学系, 助教 (40624995)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2013: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2011: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
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| Keywords | 低酸素 / 口腔扁平上皮癌 / 抗腫瘍免疫 / HIF-1α / NK細胞 / LAK細胞 |
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| Research Abstract |
NK cells are essential effectors of antitumor immune responses, but the mechanism by which hypoxia regulates NK-mediated killing of OSC cells is poorly understood. In this study, we demonstrate that hypoxia impairs OSC susceptibility to NK-mediated lysis and these effects were decreased by knock-down of HIF-1a expression. The surface expression levels of MICA, CD54 and CD58 of OSC cells and NKG2D, CD11a and CD54 of NK-92 cells were decreased and the binding of target cells to NK cells was prohibited under hypoxic conditions. Furthermore,OSC cells secreted higher levels of some immunosuppressive cytokines under hypoxic conditions. Hypoxia did not influence the ability of NK cells to degranulate in response to OSC cells, though decreased the proportion of IFN-r expressing NK-92 cell and the secretion of IFN-r into culture medium. These results suggest that hypoxia regulate the potential of both OSC cells and NK cells and attenuate antitumor immune responses by NK cells.
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Report
(4 results)
Research Products
(8 results)
