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Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
Published on: October 20, 2016
TREM1 unleashes immunosuppression in glioma: targeting macrophage polarization as a new therapeutic vulnerability
Chao Zhang1, Da Teng2, Chao Wang1
1Department of Neurosurgery, The Affliated Chuzhou Hospital of Anhui Medical University, The First People's Hospital of Chuzhou, Chuzhou, China.
Background:
Tumor-associated macrophages (TAMs) represent the predominant immune cell subset within the glioma tumor microenvironment (TME). This study aims to investigate the clinical significance of TAM-related TREM1 in glioma and its potential mechanism in promoting malignant progression.
Methods:
Bioinformatics analyses were employed to assess the expression pattern and prognostic value of TREM1 in glioma. Single-cell sequencing, immunohistochemistry, and immunofluorescence were used to determine the cellular origin and spatial distribution of TREM1. Using a co-culture model with TREM1 silenced, the potential impact of knocking down TAM-related TREM1 on suppressing malignant progression of glioma and its effect on macrophage polarization markers were evaluated through CCK-8, Transwell, wound healing assays, western blot, and flow cytometry.
Results:
TREM1 expression was upregulated in glioma and enriched in subtypes with higher malignant potential, indicating its role as a potential prognostic biomarker. TREM1 was closely associated with M2-type macrophages and promoted their polarization towards the M2 subtype. Knockdown of TREM1 in macrophages reduced the proliferation, invasion, and migration capabilities of glioma cells.
Conclusion:
TREM1 serves as a TAM-related oncogenic biomarker that facilitates malignant progression and immune suppression in glioma by promoting M2 macrophage polarization. Targeting TREM1 may offer a novel strategy to enhance the efficacy of immunotherapy for glioma.
