Language
English
Publication Date
1-13-2025
Journal
Cancer Cell
DOI
10.1016/j.ccell.2024.12.006
PMID
39753140
Abstract
Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis. PCs secrete immunoglobulin G (IgG), which stimulates GSC proliferation via the IgG-FcγRIIA-AKT-mTOR axis. Disruption of IgG-FcγRIIA paracrine communication inhibits GSC proliferation and self-renewal. Glioblastoma-infiltrating PCs are recruited to GSC niches via CCL2-CCR2 chemokine program. GSCs further derive pro-proliferative signals from broadly utilized monoclonal antibody-based immune checkpoint inhibitors via FcγRIIA signaling. Our data generate an atlas of B-lineage cells in glioblastoma with a framework for combinatorial targeting of both tumor cell-intrinsic and microenvironmental dependencies.
Keywords
Glioblastoma, Humans, Neoplastic Stem Cells, Immunoglobulin G, Plasma Cells, Brain Neoplasms, Animals, Mice, Tumor Microenvironment, Cell Proliferation, Receptors, IgG, Lymphocytes, Tumor-Infiltrating, Signal Transduction, Cell Line, Tumor, Receptors, CCR2, FcγRIIA, glioblastoma, glioblastoma stem cell, plasma cell, single-cell B cell receptor-seq, single-cell RNA-seq
Published Open-Access
yes
Recommended Citation
Gao, Jiancheng; Gu, Danling; Yang, Kailin; et al., "Infiltrating Plasma Cells Maintain Glioblastoma Stem Cells Through IgG-Tumor Binding" (2025). Faculty, Staff and Students Publications. 6475.
https://digitalcommons.library.tmc.edu/baylor_docs/6475