The research of targeting tumor-associated macrophages, a new combination therapy strategy by macrophage polarization and immune checkpoint blockade
| Project/Area Number |
21K15586
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | National Center for Child Health and Development |
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Principal Investigator |
Hu Xin 国立研究開発法人国立成育医療研究センター, 移植免疫研究室, 研究員 (40868965)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | PD-L1 / Tumor microenvironment / CD11b+ cells / β-glucan / tumor microenvironment / CD11b cells / TIL / PD-1/PD-L1 / TAM / Tils / Macrophage |
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| Outline of Research at the Start |
TAMs function is suppressing the T-cell mediated anti-tumor immune response.β-glucan converts polarized alternatively immunosuppressive TAMs into activated phenotype. We will focus on how to improve the efficacy of the β-glucanwith the anti-PD-1/PD-L1mAb treatment and their mechanism.
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| Outline of Final Research Achievements |
One of the major functions of tumor-recruited CD11b+ cells is suppressing the T-cell mediated anti-tumor immune response. β-glucan could enhance tumor-recruited CD11b+ cells anti-tumor effects. However, β-glucan could increase PD-1/PD-L1 expression on CD11b+ cells. These effects may be reversed by PD-1/PD-L1 block therapy. In the present study, we focused on the PD-1/PD-L1 blocked therapy enhanced the β-glucan antitumor effects, and their synergistic effects mechanism. In our mouse melanoma model, PD-L1 blocking antibody with β-glucan synergized tumor regression. After treatment with β-glucan and anti-PD-L1 antibody, tumor infiltrating leukocyte (TILs) were not only competent for the T cell function and CTL population but also showed enhanced tumor-recruited CD11b+ myeloid cells activity.PD-1/PD-L1 blocked therapy enhanced the β-glucan antitumor effects via blockade the tumor-recruited CD11b+ cells immune checkpoints.
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| Academic Significance and Societal Importance of the Research Achievements |
Immunotherapy aimed at reversing the phenotype of tumor-recruited CD11b+ cells to promote the anti-tumor phenotype is a promising area of research, and further investigation is needed to establish its clinical value in cancer immunotherapy.
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Report
(3 results)
Research Products
(7 results)
