| Project/Area Number |
26670508
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Hosoi Hajime 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20238744)
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| Co-Investigator(Kenkyū-buntansha) |
家原 知子 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (20285266)
桑原 康通 京都府立医科大学, 医学(系)研究科(研究院), 講師 (30590327)
菊地 顕 京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (40453104)
宮地 充 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40584983)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 小児がん / 免疫療法 / 横紋筋肉腫 / 免疫チェックポイント / PD-L1 / PD-1 / 融合遺伝子 |
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| Outline of Final Research Achievements |
Novel therapeutic strategy is required to cure patients with PAX3-FOXO1 positive metastatic rhabdomyosarcoma (RMS). Programmed cell death 1 ligand 1 (PD-L1) plays a major role in suppressing the immune system. Here, we examined the relationship between PAX3-FOXO1 fusion gene and PD-L1 expression to explore the possibility of using anti-PD-1 antibody as treatment for metastatic RMS.
Four PAX3-FOXO1-positive RMS cell lines (RM2, Rh4, Rh30, Rh41) were used. The PD-L1 expression was determined by real-time qPCR and flow cytometry. The PD-L1 expressions of the Rh30 and the RM2 cell line were high among the four cell lines. PAX3-FOXO1 knockdown resulted in decrease in cell-surface expression of PD-L1 in Rh30 and RM2 cells.
Our results show that PAX3-FOXO1 plays a role in PD-L1 mediated immune escape. Anti-PD-1 antibody can be a novel therapeutic strategy against PAX3-FOXO1-positive RMS.
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