ArticleCell communication and signaling : CCS2024
Knockdown of trem2 promotes proinflammatory microglia and inhibits glioma progression via the JAK2/STAT3 and NF-κB pathways.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Uncovering the biological mechanisms of TREM2 with molecular simulations: A comprehensive review and perspective.Progress in biophysics and molecular biology · 2026Review
- TREM2 in glioma: Reprogramming the immune microenvironment from mechanistic understanding to clinical translation (Review).Molecular medicine reports · 2026Review
- Trem2 regulates macrophage phenotype via the JAK2/STAT3 signaling pathway to ameliorate ventricular remodeling after acute myocardial infarction.Molecular biology reports · 2026Article
- Discovery of a non-canonical TREM2-S100A9 axis that drives pro-tumorigenic macrophage polarization and sensitizes ovarian clear cell carcinoma to IL-17 blockade.Cell death discovery · 2026Article
- Targeting m6A-SCG2-TAMs axis overcomes 5-FU resistance in colorectal cancer via a multi-omics model.NPJ digital medicine · 2026Article
- [Mechanism of mesenchymal stem cell-derived exosomes in alleviating hypoxia/re-oxygenation-induced injury of oligodendrocytes].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Article
- Focused ultrasound for cellular mechanoactivation and nanomedicine delivery in cancer.Biomedical microdevices · 2026Review
- Oral Diseases and Brain Pathologies: A Systematic Review with Narrative Synthesis of Clinical, Neuroimaging, and Mechanistic Evidence.Biomedicines · 2026Review
- Decoding TREM2 Signaling Pathways: Linking Macrophage Glycolysis to Inflammatory Diseases in the CNS.Neurology(R) neuroimmunology & neuroinflammation · 2026Review
- Sex Differences in Metabolite-Immune Circuits of Neuroinflammation.Immunological reviews · 2026Review
- Nervous and immune system crosstalk shapes cancer progression and treatment response.Discover oncology · 2026Review
- Inflammation in hepatocellular carcinoma progression: a "Single Wick, dual interwoven strands" regulatory framework.Frontiers in immunology · 2026Review
- Natural Medicines Modulating Tumor Perineural Invasion: Regulatory Mechanisms and Therapeutic Potential.Drug design, development and therapy · 2026Review
- Biomimetic PD-1-MSCs membrane-engineered nanoparticles for enhanced blood-brain barrier penetration and anti- glioma therapy.Frontiers in immunology · 2026Article
- Innate immune signaling-driven myeloid remodeling in cancer: inflammatory amplification, immune suppression, and therapeutic targeting.Frontiers in immunology · 2026Review
- Exploring tumor-associated macrophages in glioblastoma: from diversity to therapy.NPJ precision oncology · 2025Review
- Ganoderma lucidum polysaccharide attenuates retinal ischemia-reperfusion injury by regulating microglial M1/M2 polarization, suppressing neuroinflammation and inhibiting JAK2/STAT3 pathway.Biochemistry and biophysics reports · 2025Article
- TREM2 Impairs Glycolysis to Interrupt Microglial M1 Polarization and Inflammation via JAK2/STAT3 Axis.Cell biochemistry and biophysics · 2025Article
- Engineered oncolytic virus coated with anti-PD-1 and alendronate for ameliorating intratumoral T cell hypofunction.Experimental hematology & oncology · 2025Article
- TREM2 in MASH: integrating lipid metabolism and immune response.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
backgroundIn the tumor immune microenvironment (TIME), triggering receptor expressed on myeloid cells 2 (trem2) is widely considered to be a crucial molecule on tumor-associated macrophages(TAMs). Multiple studies have shown that trem2 may function as an immune checkpoint in various malignant tumors, mediating tumor immune evasion. However, its specific molecular mechanisms, especially in glioma, remain elusive.
methodsLentivirus was transfected to establish cells with stable knockdown of trem2. A Transwell system was used for segregated coculture of glioma cells and microglia. Western blotting, quantitative real-time polymerase chain reaction (qRT‒PCR), and immunofluorescence (IF) were used to measure the expression levels of target proteins. The proliferation, invasion, and migration of cells were detected by colony formation, cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU) and transwell assays. The cell cycle, apoptosis rate and reactive oxygen species (ROS) level of cells were assessed using flow cytometry assays. The comet assay and tube formation assay were used to detect DNA damage in glioma cells and angiogenesis activity, respectively. Gl261 cell lines and C57BL/6 mice were used to construct the glioma orthotopic transplantation tumor model.
resultsTrem2 was highly overexpressed in glioma TAMs. Knocking down trem2 in microglia suppressed the growth and angiogenesis activity of glioma cells in vivo and in vitro. Mechanistically, knockdown of trem2 in microglia promoted proinflammatory microglia and inhibited anti-inflammatory microglia by activating jak2/stat1 and inhibiting the NF-κB p50 signaling pathway. The proinflammatory microglia produced high concentrations of nitric oxide (NO) and high levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1β, and caused further DNA damage and promoted the apoptosis rate of tumor cells.
conclusionsOur findings revealed that trem2 in microglia plays a significant role in the TIME of gliomas. Knockdown of trem2 in microglia might help to improve the efficiency of inhibiting glioma growth and delaying tumor progression and provide new ideas for further treatment of glioma.
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