2021 Fiscal Year Research-status Report
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 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, リサーチアソシエイト (40868965)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Keywords | CD11b cells / β-glucan / PD-L1 / TIL / tumor microenvironment |
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| Outline of Annual Research Achievements |
In the tumor microenvironment,tumor-associated macrophages could suppress the T-cell mediated anti-tumor immune response.We found β glucan enhance inflammation cytokine（TNF-α，IL-12, IL-6, IL-1β）and immune checkpoint PD-1 and PD-L1 in naive mouse peritoneal macrophage.β glucan combined with αPD-L1Ab synergistically enhanced the anti-melanoma response.We isolated TILs and peritoneal macrophage,we found that β-glucan with αPD-L1Ab could enhance cytokine TNF-α，IL-12, IL-1βand immune checkpoint PD-1 and PD-L1.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Tumor models: We established B16F10 melanoma and C26 colon tumor model.
β-glucan with/without anti-PD-L1mAb anti-tumor effect in tumor model:We found β-glucan and anti-PD-L1mAb treatment synergistically enhanced the anti-melanoma response.
The tumor-recruited CD11b+ cells function:
β-glucan with anti-PD-L1 mAb increased the tumor-recruited CD11b+ cells cytokines; β-glucan increased the TADC’s CD40, CD80, CD86, MHC-II;β-glucan with anti-PD-L1 mAb increased the tumor infiltrating lymphocytes cytokines and checkpoint marker.
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| Strategy for Future Research Activity |
（A）Analysis of Tumor-infiltrating lymphoid T cells cytolytic particles in vivo. （B）Analysis the effects of β-glucan with/without anti-PD-L1mAb and verification mechanisms in vitro.（C）Analysis of β-glucan with/without anti-PD-L1mAb effect in tumor bearing mouse spleen
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Research Products
(2 results)
