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Updated: Jun 4, 2025
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding
Jiancheng Gao1, Danling Gu2, Kailin Yang3
1National Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu 211166, China; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China; Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Plasma cells (PCs) in glioblastoma tumors drive cancer stem cell proliferation via IgG signaling. Targeting this pathway may offer new glioblastoma treatment strategies.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Biology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor driven by glioblastoma stem cells (GSCs).
- The role of B-lineage immune cells, particularly plasma cells (PCs), in GBM is largely unknown.
- Understanding the tumor microenvironment is crucial for developing effective GBM therapies.
Purpose of the Study:
- To investigate the presence, characteristics, and functional role of B-lineage cells, especially PCs, within the GBM tumor microenvironment.
- To elucidate the mechanisms by which PCs influence glioblastoma stem cell behavior and proliferation.
- To identify potential therapeutic targets within the PC-GSC interaction axis.
Main Methods:
- Single-cell RNA sequencing and B cell receptor sequencing of tumor-infiltrating B-lineage cells from glioblastoma patients.
- Analysis of plasma cell enrichment, somatic hypermutation levels, and correlation with patient prognosis.
- Investigation of the signaling pathway involving immunoglobulin G (IgG), FcγRIIA, AKT, and mTOR in GSC proliferation.
- Characterization of PC recruitment mechanisms using the CCL2-CCR2 chemokine pathway.
- Assessment of GSC response to immune checkpoint inhibitors via FcγRIIA signaling.
Main Results:
- Plasma cells are aberrantly enriched in glioblastoma, exhibit low somatic hypermutation, and associate with poor prognosis.
- Secreted IgG from PCs stimulates GSC proliferation through the IgG-FcγRIIA-AKT-mTOR pathway.
- Blocking IgG-FcγRIIA interaction inhibits GSC proliferation and self-renewal.
- Glioblastoma-infiltrating PCs are recruited to GSC niches via the CCL2-CCR2 chemokine axis.
- Glioblastoma stem cells utilize FcγRIIA signaling to receive pro-proliferative signals, including from antibody-based immune checkpoint inhibitors.
Conclusions:
- Plasma cells represent a significant component of the B-lineage infiltrate in glioblastoma, contributing to tumor progression.
- The IgG-FcγRIIA-AKT-mTOR axis is a critical pathway for GSC proliferation, driven by tumor-infiltrating PCs.
- Targeting the interaction between plasma cells and glioblastoma stem cells, potentially via FcγRIIA blockade, offers a promising therapeutic strategy.
- Understanding the B-cell landscape in glioblastoma provides a framework for combinatorial therapies targeting tumor-intrinsic and microenvironmental dependencies.
