Macrophage lipid signaling drives glioblastoma invasion and represents a therapeutic vulnerability.

In mouse models and human GBM samples, tumor cells engage and reprogram tumor-associated microglia/macrophages via CSF1R–PI3K signaling, driving invasion through secreted LPCs and LPAs.

• Why it matters: GBM’s diffuse infiltration limits complete resection, but the lipid-mediated mechanisms linking myeloid cells to invasion are incompletely understood.
• What they did: The study integrated single-cell transcriptomics, spatial lipidomics, and functional perturbation to map a CSF1R–PI3K axis and quantify bioactive lipid secretion, including lysophosphatidylcholines (LPCs) and lysophosphatidic acids (LPAs).
• The result: Disrupting the myeloid–GBM axis reduces lipid secretion and suppresses invasion, while targeting LPA–LPAR or YAP/TAZ signaling further constrains invasion in a context-dependent manner.