The role of LILRB4 on MDSC-mediated immunosuppression in tumor environment

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16705
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Tohoku University
• Principal Investigator: SU Mei-Tzu 東北大学, 加齢医学研究所, 助教 (00812116)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: MDSC / LILRB4 / gp49B / immunosuppression / metastasis

Outline of Final Research Achievements

Myeloid-derived suppressor cells (MDSCs) are involved in tumor-associated immunosuppression, and dominate tumor progression and metastasis. In this study, we report that the leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4, murine ortholog gp49B) orchestrates the polarization of MDSCs to exhibit pro-tumor phenotypes. Gp49B－/－ MDSCs inhibited pro-tumor immune responses such as activation of Treg cells, promotion of cancer cell migration, and stimulation of tumor angiogenesis. Treatment of wild-type tumor-bearing mice with gp49B－/－ M-MDSCs reduced cancer metastasis. Furthermore, gp49B knockout affected plasma exosome composition in terms of increased anti-tumor microRNAs expression. Collectively, our findings reveal that LILRB4/gp49B promotes MDSC-mediated tumor metastasis by regulating the M2-polarization of MDSCs and suppressing the secretion of miR-1 family miRNAs, which facilitate tumor migration and invasion.

Free Research Field

Oncolmmunology

Academic Significance and Societal Importance of the Research Achievements

Immune checkpoint inhibitors (ICIs) are used to enhance the antitumor immune response. Several patients do not respond to ICIs due to MDSC-mediated immune escape. Investigation of LILRB4 on how to contribute to MDSC-mediated immunosuppression could provide a new approach for ICI combination therapy.