The research of targeting tumor-associated macrophages, a new combination therapy strategy by macrophage polarization and immune checkpoint blockade

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15586
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: National Center for Child Health and Development
• 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)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: PD-L1 / Tumor microenvironment / CD11b+ cells / β-glucan

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.

Free Research Field

腫瘍診断お よ び 治療学関連

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.