| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Outline of Final Research Achievements |
MICA is expressed on the surface of hepatocellulara carcinoma (HCC) cells and is a target of NK cells, but HCC cells cleave MICA to evade NK cell attack. 1) We identified ADAM9/10/17 as MICA cleaving enzymes. 2) MICA expression was upregulated in HCC tissues, but MICA cleavage resulted in low NK cell invasion into the tissues. 3) Screening of ADAM9 inhibitors identified two leukotriene antagonists and an acyclic retinoid. 4) ADAM9 also cleaved membrane PD-L1 and evaded the acquired immunity mechanism. These findings suggest that ADAM9 inhibition may be useful for the treatment of HCC and prevention of hepatocarcinogenesis by stimulating innate and acquired immunity against HCC.
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