2. Academic Validation
  3. TREM2 inhibition triggers antitumor cell activity of myeloid cells in glioblastoma

TREM2 inhibition triggers antitumor cell activity of myeloid cells in glioblastoma

  • Sci Adv. 2023 May 12;9(19):eade3559. doi: 10.1126/sciadv.ade3559.
Rui Sun 1,  Rowland Han 1,  Colin McCornack 1,  Saad Khan 1,  G Travis Tabor 2,  Yun Chen 2 3,  Jinchao Hou 3,  Haowu Jiang 4,  Kathleen M Schoch 2 5,  Diane D Mao 1,  Ryan Cleary 1,  Alicia Yang 1,  Qin Liu 4,  Jingqin Luo 6 7,  Allegra Petti 1 8 9,  Timothy M Miller 2 5,  Jason D Ulrich 2 5,  David M Holtzman 2 5 10,  Albert H Kim 1 2 8 9 11
Affiliations

Affiliations

  • 1 Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA.
  • 2 Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
  • 3 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  • 4 Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA.
  • 5 Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO, USA.
  • 6 Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
  • 7 Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
  • 8 Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
  • 9 The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
  • 10 Center for Science and Engineering of Living Systems, Washington University in St. Louis, St. Louis, MO, USA.
  • 11 Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.
PMID: 37172094 DOI: 10.1126/sciadv.ade3559
Abstract

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.

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