Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell surface receptor of the immunoglobulin superfamily. The TREM2 is found in various tissue macrophages, such as CNS microglia, bone osteoclasts, alveolar, peritoneal and intestinal macrophages. TREM2 is also present on cultured bone marrow-derived macrophages and monocyte-derived dendritic cells. Some research have identified a rare variant of TREM2 that is a risk factor for Alzheimer disease (AD), which is the most common form of late-onset dementia.The extracellular region of TREM2 contains a single immunoglobulin superfamily domain and binds polyanionic ligands, such as bacterial lipopolysaccharide (LPS) and phospholipids8. Upon ligand binding, TREM2 transmits intracellular signals through an adaptor, DAP12 (also known as TYRO protein tyrosine kinase-binding protein (TYROBP)), which is associated with the transmembrane region of TREM2 and which recruits the protein tyrosine kinase SYK through its cytosolic immunoreceptor tyrosine-based activation motifs (ITAMs). TREM2 is a pro-tumorigenic marker of tumor-infiltrating macrophages in mouse models and human tumors that can be targeted to curb tumor growth and improve the efficacy of checkpoint blockade therapy while remodeling the landscape of tumor-infiltrating macrophages.

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