Decoding the Prognosis-Related S100A9^high Monocyte in Glioblastoma Using Single-Cell and Spatial Transcriptome...

Area of Science:

• Neuro-oncology
• Immunology
• Single-cell genomics

Background:

• Monocytes and macrophages are key immune cells in human glioblastoma, influencing tumor progression.
• The heterogeneity within the monocyte population in glioblastoma is not fully understood.

Purpose of the Study:

• To investigate the heterogeneity and function of monocytes in glioblastoma.
• To characterize distinct glioblastoma subtypes based on ligand-receptor networks.

Main Methods:

• Comprehensive analysis using single-cell RNA sequencing (scRNA-seq).
• Spatial transcriptome sequencing combined with immunofluorescence assays.
• In vitro T cell co-culture assays.

Main Results:

• Identified three glioblastoma subtypes; the C3 subtype showed a higher proportion of S100A9^high monocytes associated with poor prognosis.
• S100A9^high monocytes were spatially located near M2 macrophages, exhausted CD8+ T cells, and endothelial cells.
• S100A9^high monocytes produced immunosuppressive IL-10, ROS, and iNOS, potentially impairing T cell function.

Conclusions:

• Deciphered monocyte heterogeneity in glioblastoma.
• Identified S100A9^high monocytes as a novel subset linked to poor prognosis.
• These monocytes contribute to an immunosuppressive, pro-tumorigenic microenvironment in glioblastoma.