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TREM2 inhibition triggers anti-tumor cell activity of myeloid cells in glioblastoma

ABSTRACT: TREM2 inhibition triggers anti-tumor cell activity of myeloid cells in glioblastoma

PROVIDER: PRJNA939548 | ENA |

REPOSITORIES: ENA

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TREM2 inhibition triggers anti-tumor cell activity of myeloid cells in glioblastoma [RNAseq]

Project description:The prevailing view is that myeloid cells in the tumor microenvironment (TME) are immunosuppressive and promote glioblastoma (GBM) progression. However, myeloid cells have the functional plasticity to restrict or support tumor cell growth. TREM2 plays important roles in brain microglial function in neurodegenerative diseases, but the role of TREM2 in the GBM TME has not been examined. We found 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 GBM patients. TREM2 loss of function in human macrophages and mouse myeloid cells increased tumoricidal capacity. TREM2 in myeloid cells restricts IFNγ-induced immunoactivation and proinflammatory polarization. In orthotopic mouse GBM models, Trem2-/- mice and mice with acute brain Trem2 reduction demonstrate survival benefit. Trem2 inhibition reprograms myeloid phenotypes and increases PD-1+CD8+ T cells in the TME. Trem2 deficiency enhances the effectiveness of anti-PD-1 treatment and may represent a therapeutic strategy for GBM patients.

2023-05-12 | GSE226172 | GEO

TREM2 inhibition triggers anti-tumor cell activity of myeloid cells in glioblastoma [scRNA]

2023-05-12 | GSE226292 | GEO

TREM2 inhibition triggers anti-tumor cell activity of myeloid cells in glioblastoma [scRNA]

Project description:TREM2 inhibition triggers anti-tumor cell activity of myeloid cells in glioblastoma [scRNA]

| PRJNA939552 | ENA

TREM2 inhibition triggers anti-tumor cell activity of myeloid cells in glioblastoma [RNAseq]

Project description:TREM2 inhibition triggers anti-tumor cell activity of myeloid cells in glioblastoma [RNAseq]

| PRJNA939127 | ENA

TREM2 inhibition triggers antitumor cell activity of myeloid cells in glioblastoma.

Project description: Not available

| S-EPMC10181199 | biostudies-literature

TREM2 blockade modifies the tumor myeloid landscape enhancing anti-PD-1 immunotherapy

Project description:Checkpoint immunotherapy unleashes T cell effector functions that control tumor growth, but can be undermined by myeloid cells that induce immunosuppression. TREM2 is a myeloid surface receptor that binds lipids and transmits intracellular signals through protein-tyrosine phosphorylation known to sustain microglial responses during Alzheimer’s disease. Intriguingly, TREM2 expression has recently been noted in tumor-infiltrating macrophages. We found that Trem2–/– mice are more resistant to growth of sarcoma, colorectal and mammary cancer cells than wild-type mice and are more responsive to anti-PD-1 immunotherapy. Furthermore, treatment with anti-TREM2 mAb curbed tumor growth and led to complete tumor regression when combined with anti-PD-1. scRNA-seq revealed that both constitutive TREM2 deficiency and anti-TREM2 are associated with relatively scant representation of MRC1+ and CX3CR1+ subsets in the macrophage tumor infiltrate, paralleled by expansion of subsets expressing immunostimulatory molecules. These changes were associated with improved T cell responses. TREM2 expression was evident in tumor macrophages in over 200 human cancer cases examined and inversely correlated with prolonged survival for two types of cancer. Thus, TREM2 is a promising target to modify tumor-infiltrating myeloid cells and effectively augment checkpoint immunotherapy.

2020-08-13 | GSE151710 | GEO

TREM2 inhibition triggers anti-tumor cell activity of myeloid cells in glioblastoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-05-12 | GSE226293 | GEO

Effect of myeloid specific Trem2 knockout in hepatocellular carcinoma after anti-PD-1 therapy [ChIP-seq]

Project description:Immune-checkpoint blockade (ICB) therapies have transformed the treatment landscapes of solid malignancies, including hepatocellular carcinoma (HCC), which is currently the sixth most common cancer and the third leading cause of cancer death worldwide. Despite unprecedented success in clinical trials, the immunosuppressive tumor microenvironment constructed by tumor cells restricts the responsiveness of ICB therapies to a minority of patients. Triggering receptor expressed on myeloid cells-2 (TREM2) counteracts inflammation and maintains metabolic fitness in myeloid cells. Emerging single-cell RNA sequencing data in different types of tumors have identified the significance of TREM2+ myeloid cells in tumor development and ICB resistance. In this study, we aimed to investigate the potential role of TREM2 in HCC ICB resistance.

2026-04-29 | GSE291234 | GEO

Effect of myeloid specific Trem2 knockout in hepatocellular carcinoma after anti-PD-1 therapy [RNA-seq]

2026-04-29 | GSE291032 | GEO

scRNAseq profiling of myeloid and lymphoid cells in total Trem2+/+ and Trem2-/- lungs

Project description:scRNAseq profiling of FACS-sorted myeloid enriched (DAPI-CD45+Ly6G- CD3e-CD11b+ and/or CD11c+) and lymphoid enriched (DAPI-CD45+Ly6G- CD3e+) fractions purified from murine lungs bearing KP-GFP tumor lesions (28 days after tumor delivery intravenously) isolated from Trem2+/+ and Trem2-/- animals

2022-09-01 | GSE184304 | GEO

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