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Isolation of Group 2 Innate Lymphoid Cells from Mouse Nasal Mucosa to Detect the Expression of CD226
Published on: May 10, 2022
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Modulating CD226 and PD-(L)1 pathways improves CMV-specific CD8＋T cell responses in the absence of IL-2
Hye-In Sim1, Yunju Jo1, Hyejin Ahn2
1Chemical and Biological Integrative Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792; Department of Life Sciences, Korea University, Seoul 02481, Korea.
BMB Reports
|June 11, 2025
Summary
Modulating immune checkpoints PD-L1 and CD226 can enhance cytomegalovirus (CMV)-specific T cell function. This approach boosts T cell proliferation and memory formation, offering a promising immunotherapy strategy for glioblastoma (GBM).
Area of Science:
- Immunology
- Cancer Immunotherapy
- T Cell Biology
Background:
- Glioblastoma (GBM) tumors often express cytomegalovirus (CMV) antigens.
- CMV-specific CD8+ T cells are promising for GBM adoptive immunotherapy due to their tumor reactivity.
- The GBM microenvironment poses immunosuppressive challenges, limiting T cell function.
Purpose of the Study:
- To investigate strategies for overcoming immunosuppression in the GBM microenvironment.
- To assess the potential of modulating immune checkpoint pathways (PD-L1, CD226) to enhance T cell function.
Main Methods:
- CMV-specific CD8+ T cells were stimulated with antigen, with or without IL-2.
- Immune checkpoint blockade (anti-PD-L1) and agonism (anti-CD226) were employed.
- T cell expansion, avidity (tetramer staining), memory phenotype (CD62L), and function (IFN-γ) were analyzed.
Main Results:
- Antigen stimulation plus IL-2 robustly expanded high-avidity T cells and central memory cells (TCM).
- PD-L1 blockade alone enhanced T cell expansion and preserved memory markers.
- Combined PD-L1 blockade and CD226 agonism significantly boosted proliferation, IFN-γ production, and TCM enrichment, comparable to IL-2 conditions.
Conclusions:
- Simultaneous modulation of PD-L1 and CD226 pathways restores CMV-specific T cell function in immunosuppressive environments.
- This dual-targeting strategy offers a potent approach to enhance T cell-based immunotherapy for glioblastoma.
- The findings provide a promising avenue for improving TCR-T cell efficacy in cytokine-deprived tumors.
