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Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
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Complement Factor H Is an ICOS Ligand Modulating Tregs in the Glioma Microenvironment
Karolina I Smolag1, Jakub Olszowka1, Rebecca Rosberg2
1Section of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Malmö, Sweden.
Cancer Immunology Research
|October 8, 2024
Summary
Complement factor H (FH) promotes regulatory T cell (Treg) survival and function in glioma, contributing to an immunosuppressive tumor microenvironment and worse patient prognosis. Evaluating FH may predict immunotherapy response.
Area of Science:
- Neuro-oncology
- Immunology
- Molecular Biology
Background:
- Glioma survival rates remain poor despite advances in immunotherapy, partly due to an immunosuppressive tumor microenvironment.
- Regulatory T cells (Tregs) are key mediators of immune tolerance within the glioma microenvironment.
Purpose of the Study:
- To investigate the role of complement factor H (FH) in regulating Tregs within the glioma microenvironment.
- To determine the impact of FH on Treg function, glioma progression, and patient prognosis.
Main Methods:
- Investigated FH as an ICOS ligand and its effect on Treg survival, function, and cytokine secretion (TGFβ, IL10).
- Assessed FH production by glioma cells in human and mouse samples.
- Analyzed FH expression in relation to Treg presence and patient prognosis using database investigations.
- Utilized a mouse glioma model to evaluate the in vivo effect of FH knockdown on Tregs and survival.
Main Results:
- FH was identified as an ICOS ligand that enhances Treg survival and function, promoting immunosuppression.
- FH induces secretion of TGFβ and IL10 by Tregs, suppressing T-cell proliferation.
- Glioma cells were found to directly produce FH.
- Upregulated FH expression correlated with increased Treg presence and poorer glioma patient prognosis.
- FH knockdown in a mouse model reduced ICOS+ Tregs and showed a trend towards prolonged survival.
Conclusions:
- FH plays a critical role in fostering an immunosuppressive glioma microenvironment by promoting Treg accumulation and function.
- FH is a potential biomarker for predicting glioma prognosis and response to immunotherapy.
- Targeting FH or Tregs could represent a novel therapeutic strategy for glioma.
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