| Project/Area Number |
16K19974
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory surgery
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| Research Institution | Chiba University |
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Principal Investigator |
Takami Mariko 千葉大学, 大学院医学研究院, 助教 (60770906)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | NKT細胞 / 免疫療法 / AhRシグナル / 肺癌 / 免疫学 / 免疫治療 |
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| Outline of Final Research Achievements |
To improve our current iNKT cell based immunotherapy for lung cancer, I focused on aryl hydrocarbon receptor (AhR) signaling. I hypothesized that AhR signaling suppresses an immune checkpoint molecule, PD-L1/PD-L2 expression on iNKT cells, thus augmenting anti-tumor effect of iNKT cells.
PD-L1 expression on iNKT cells was downregulated in the presence of AhR ligand. These data suggest that AhR signaling negatively regulates PD-L1 expression. However, AhR signaling did not affect anti-tumor effect of iNKT cells. When monocytes derived DCs (moDCs) were cultured in the presence of AhR agonist, moDCs downregulated PD-L1/PD-L2 expression. Moreover, AhR agonist-treated moDCs induced enhanced cytokine production of iNKT cells. These data indicate that AhR agonist enhances moDC function to induce greater cytokine production by iNKT cells. AhR agonist treatment could be combined with our current iNKT cell based immunotherapy as next generation of combination therapy.
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