TREM2 (Triggering Receptor Expressed On Myeloid Cells 2)

Conversely, intrathecal overexpression of the TREM2 gene can also induce abnormal pain responses. TREM2 may be the key gene involved in the hyperalgesia induced by excessive activation of spinal microglia under pathological conditions of bone cancer, which depends on the phosphorylation of the PI3K/Akt signaling axis.

Similarly, intracerebroventricular (ICV) administration of Sox10 promoter-driven AAV-Bmp4 efficiently ameliorated AD progression. Collectively, these findings uncover an OPC-microglia crosstalk that governs immune surveillance in AD, highlighting COP-targeted enhancement of Bmp4 as a promising avenue for interventions aimed at reinforcing early neuroprotective responses.

Additionally, TREM2 enhanced gemcitabine sensitivity by lowering the gemcitabine IC50 and promoting gemcitabine-induced apoptosis. Collectively, TREM2 exerts tumor-suppressive functions in cholangiocarcinoma and enhances chemotherapy sensitivity, suggesting its potential as a therapeutic target and prognostic biomarker.

Aggressive LDL lowering reverses inflammasome activation and induces pro-resolving changes in macrophages in Jak2VF MPN, halting atherosclerosis progression and promoting features of plaque stabilization. These findings suggest that aggressive LDL cholesterol lowering could reverse atherosclerotic cardiovascular disease (ACVD) risk in individuals with JAK2VF CHIP or MPN.

This contrasts sharply with its metabolic role in benign prostatic hyperplasia and its protective role in non-malignant renal injury. We also consider the translational potential of TREM2 as a prognostic biomarker (specifically urine detection) and as a therapeutic target to reverse immunotherapy resistance.

Genetic ablation of Trem2 or pharmacologic targeting with antisense oligonucleotides suppress paclitaxel-induced breast cancer lung metastasis in vivo. Collectively, our findings demonstrate that paclitaxel, but not nab-paclitaxel, stimulates TREM2 expression and expands TREM2+ macrophages, suggesting that TREM2 targeting could enhance paclitaxel efficacy while limiting metastasis.

These effects of Cyst-C are abolished by a cell-type-specific deletion (Cx3cr1TREM2-/-) or mutation of TREM2 (TREM2R47H) or Cyst-C (Cyst-CL68Q) in microglia. Together, these findings provide significant conceptual advances into cancer neuroscience and establish therapeutic avenues that are distinct from the present amyloid-lowering strategies, aiming at degrading the existing amyloid plaques for precision-targeted AD therapy.

Tumor clearance depends, in part, on FAS expression on cancer cells, revealing an IL-12-FAS axis for IL-12-armored CAR-T activity. These findings position IL-12-producing, myeloid-directed CAR-T as a broad strategy to remodel the TME and drive anti-tumor immunity for solid cancers.

Notably, the clinical agonist sotigalimab similarly enhances human CD8+ T cell migration in vitro. Our findings highlight the significance of combining GPC3-CAR-T therapy with CD40 agonist as a critical pre-requisite for eliciting reeducation of TAMs and enhancing the efficacy of CAR-T therapy in HCC.

The results of our study indicate that DKMX extracts exert their anti-neuroinflammatory effects primarily through the TREM2/Wnt/β-catenin pathway, thereby alleviating symptoms and enhancing functional outcomes in rats with PSD.

Our pilot study demonstrated the feasibility of generating high-quality, large-scale single-cell multi-omic data from the human amygdala. We observed abundant AD-associated microglia in amygdala, suggesting the possibility that the regional vulnerability of amygdala to multiple neurodegenerative disorders might be in part due to different glial composition.

TREM2 positively regulates DAP12 and forms a complex that impacts glioma development via the PI3K/AKT pathway. Targeting the TREM2/DAP12 complex presents a potential therapeutic approach for gliomas.