Genetic drivers shape TREM2-dependent myeloid responses and glioblastoma progression

Trem2 deficiency prolonged survival and reduced tumor burden in Nf1-silenced/Ras-driven murine glioblastoma, but increased tumor burden without affecting survival in PDGFB-driven glioblastoma.

• Why it matters: Genetic drivers shape the myeloid-enriched, immunosuppressive GBM microenvironment, yet how TREM2’s effects depend on tumor context and timing is unclear.
• What they did: Using de novo and orthotopic transplantable murine GBM models, immune profiling, functional assays, secretome analysis, single-cell RNA sequencing, bone marrow chimeras, and conditional Trem2 deletion, the study tested TREM2 effects across Nf1-silenced/Ras-driven versus PDGFB-driven tumors.
• The result: TREM2 was required for bone marrow-derived macrophage migration and microglial process extension toward Ras-derived, but not PDGFB-derived, tumor-conditioned medium, while both models showed impaired microglial efferocytosis; Trem2 loss shifted Nf1-silenced myeloid cells toward a more homeostatic state and deletion before implantation prolonged survival.