Abstract
Purpose:
Monocytes and macrophages are recognized as predominant immune populations in human glioblastoma, where they play vital roles in tumor progression. Despite their established significance, the heterogeneity of these cells-particularly within the monocyte compartment-remains incompletely characterized.
Methods:
We comprehensively used scRNA-seq, spatial transcriptome sequencing combined with immunofluorescence and T cell co-culture assays to illuminate the heterogeneity and function of monocyte in glioblastoma.
Results:
In this study, from the perspective of ligand-receptor networks, we have identified and characterized three distinct glioblastoma subtypes. Single-cell RNA-seq analysis further revealed that the C3 subtype with bad prognosis exhibited a higher proportion of S100A9high monocytes. Spatial transcriptomics combined with immunofluorescence assays demonstrated that these S100A9high monocytes were spatially adjacent to M2 macrophages, exhausted CD8+ T cells, and endothelial cells. In vitro T cell co-culture assays revealed S100A9high monocyte produced elevated levels of the immunosuppressive cytokine IL-10, reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS), all of which might impair T cell function and immune response. Notably, elevated abundance of S100A9high monocyte correlated with poor patient prognosis.
Conclusion:
In summary, our results deciphered the heterogeneity of monocytes in glioblastoma and identified a novel poor prognosis-associated monocyte subset, S100A9high monocytes, which foster an immunosuppressive, pro-tumorigenic microenvironment.