TREM2 inhibition triggers antitumor cell activity of myeloid cells in glioblastoma
Menée in vitro et à l'aide de modèles murins de glioblastome, cette étude met en évidence l'intérêt d'inhiber le récepteur TREM2 pour augmenter le nombre de lymphocytes T CD8+ PD-1+ dans le microenvironnement tumoral et améliorer l'efficacité des anti-PD-1
Triggering receptor expressed on myeloid cells 2 (TREM2) plays important roles in brain microglial function in neurodegenerative diseases, but the role of TREM2 in the GBM TME has not been examined. Here, we found that TREM2 is highly expressed in myeloid subsets, including macrophages and microglia in human and mouse GBM tumors and that high TREM2 expression correlates with poor prognosis in patients with GBM. TREM2 loss of function in human macrophages and mouse myeloid cells increased interferon-γ–induced immunoactivation, proinflammatory polarization, and tumoricidal capacity. In orthotopic mouse GBM models, mice with chronic and acute Trem2 loss of function exhibited decreased tumor growth and increased survival. Trem2 inhibition reprogrammed myeloid phenotypes and increased programmed cell death protein 1 (PD-1)+CD8+ T cells in the TME. Last, Trem2 deficiency enhanced the effectiveness of anti–PD-1 treatment, which may represent a therapeutic strategy for patients with GBM. TREM2 inhibition remodels myeloid cells in the glioblastoma microenvironment into a proinflammatory state, curbing tumor growth.