To investigate the characteristics of tumor-associated macrophages (TAMs) in recurrent glioblastoma (GBM) and the role of Krüppel-like factor 10 (KLF10) in these macrophages.
Approach:
Single-cell RNA sequencing: Analyzed data from 16 GBM samples to identify recurrence-associated TAMs and assess functional features.
Prognostic signature construction: Used LASSO and Cox regression to create a five-gene prognostic signature.
Co-culture system: Established a GBM cell–macrophage co-culture system to examine KLF10 induction and its effects on GBM-cell behavior.
Key Findings:
A five-gene prognostic signature was identified, including KLF10, ZFAND2A, SMAD7, GPR84, and ARHGAP12.
High KLF10 expression was associated with WHO grade, IDH mutation, MGMT promoter methylation, 1p/19q co-deletion, molecular subtype, and overall survival, with high KLF10 predicting poor prognosis.
KLF10-associated genes were connected to ECM–receptor interaction, cell-cycle pathways, and cytokine signaling.
Co-culture with GBM cells increased KLF10 expression in THP-1-derived macrophages, which in turn enhanced GBM-cell proliferation, migration, and invasion.
Interpretation:
Limitations:
The study requires further validation of KLF10 as a prognostic marker.
The mechanisms of macrophage reprogramming by tumor cells in rGBM need further exploration.
