About InVivoMAb anti-mouse TREM-2 The 178 monoclonal antibody reacts with mouse TREM-2 (the triggering receptor expressed on myeloid cell 2), a single-pass transmembrane protein also known as PLOSL2. This anti-mouse TREM-2 antibody does not cross-react with TREM-1. TREM-2 is primarily expressed by myeloid cells, infiltrating macrophages, and tissue-specific macrophages, including microglia. TREM-2 acts as a receptor for abeta 42 (a cleavage product of the amyloid beta precursor protein) and mediates its uptake and degradation in microglia. TREM-2 also binds to lipoproteins (LDL, VLDL, and HDL) and apolipoproteins (APOA1/A2, APOB, APOEs, and others) and enhances their uptake by microglial cells. TREM-2 plays a key role in the functions of microglia, such as phagocytosis, cytokines release, lipid sensing, and microglia proliferation and migration. TREM2 has both anti-inflammatory and pro-inflammatory effects. In in vivo models of Alzheimer's disease (AD), TREM2 serves as a reliable indicator of microglial activation, and mutations in TREM-2 have been associated with an increased risk of neurodegenerative diseases like AD, ALS, and Parkinson's disease (PD). Tumor-infiltrating macrophages and various types of cancer cells also express TREM2 at varying levels in cancers. TREM-2 suppresses anti-tumor immune responses by inhibiting T cell-mediated immune responses and through its effects on NK cell-mediated anti-tumor immunity. In tumor immune microenvironment (TME), TREM2 is a key regulator, and its blockade can promote the response to anti-PD1 therapy. *An engineered recombinant mouse variant of the rat IgG2a anti-mouse TREM-2 (clone 178) antibody with mouse IgG constant domains and a LALA-PG Fc silencing mutation has been shown to block TREM-2 signals in vivo in murine tumor models. BE0447 is the original 178 clone with rat IgG constant domains. InVivoMAb anti-mouse TREM-2 Specifications IsotypeRat IgG2a, κ Recommended Isotype Control(s)InVivoMAb rat IgG2a isotype control, anti-trinitrophenol Recommended Dilution BufferInVivoPure pH 7.0 Dilution Buffer ImmunogenRecombinant protein containing the ectodomain of TREM-2 fused to the constant domain of human Ig Reported ApplicationsFlow cytometry ELISA in vitro TREM-2 blockade in vivo TREM-2 blockade (see description)* FormulationPBS, pH 7.0 Contains no stabilizers or preservatives Endotoxin<2EU/mg (<0.002EU/μg) Determined by LAL gel clotting assay Purity>95% Determined by SDS-PAGE Sterility0.2 μm filtered ProductionPurified from cell culture supernatant in an animal-free facility PurificationProtein G Molecular Weight150 kDa StorageThe antibody solution should be stored at the stock concentration at 4°C. Do not freeze. Application ReferencesInVivoMAb anti-mouse TREM-2 (CLONE: 178)Sun R, Han R, McCornack C, Khan S, Tabor GT, Chen Y, Hou J, Jiang H, Schoch KM, Mao DD, Cleary R, Yang A, Liu Q, Luo J, Petti A, Miller TM, Ulrich JD, Holtzman DM, Kim AH (2023). "TREM2 inhibition triggers antitumor cell activity of myeloid cells in glioblastoma" Sci Adv 9(19):eade3559. PubMedTriggering receptor expressed on myeloid cells 2 (TREM2) plays important roles in brain microglial function in neurodegenerative diseases, but the role of TREM2 in the GBM TME has not been examined. Here, we found that 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 patients with GBM. TREM2 loss of function in human macrophages and mouse myeloid cells increased interferon-γ-induced immunoactivation, proinflammatory polarization, and tumoricidal capacity. In orthotopic mouse GBM models, mice with chronic and acute Trem2 loss of function exhibited decreased tumor growth and increased survival. Trem2 inhibition reprogrammed myeloid phenotypes and increased programmed cell death protein 1 (PD-1)+CD8+ T cells in the TME. Last, Trem2 deficiency enhanced the effectiveness of anti-PD-1 treatment, which may represent a therapeutic strategy for patients with GBM.Molgora M, Esaulova E, Vermi W, Hou J, Chen Y, Luo J, Brioschi S, Bugatti M, Omodei AS, Ricci B, Fronick C, Panda SK, Takeuchi Y, Gubin MM, Faccio R, Cella M, Gilfillan S, Unanue ER, Artyomov MN, Schreiber RD, Colonna M (2020). "TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy" Cell 182(4):886-900.e17. PubMedCheckpoint immunotherapy unleashes T cell control of tumors, but is undermined by immunosuppressive myeloid cells. TREM2 is a myeloid receptor that transmits intracellular signals that sustain microglial responses during Alzheimer's disease. TREM2 is also expressed by tumor-infiltrating macrophages. Here, we found that Trem2-/- mice are more resistant to growth of various cancers than wild-type mice and are more responsive to anti-PD-1 immunotherapy. Furthermore, treatment with anti-TREM2 mAb curbed tumor growth and fostered regression when combined with anti-PD-1. scRNA-seq revealed that both TREM2 deletion and anti-TREM2 are associated with scant MRC1+ and CX3CR1+ macrophages in the tumor infiltrate, paralleled by expansion of myeloid subsets expressing immunostimulatory molecules that promote improved T cell responses. TREM2 was expressed in tumor macrophages in over 200 human cancer cases and inversely correlated with prolonged survival for two types of cancer. Thus, TREM2 might be targeted to modify tumor myeloid infiltrates and augment checkpoint immunotherapy.Turnbull IR, Gilfillan S, Cella M, Aoshi T, Miller M, Piccio L, Hernandez M, Colonna M (2006). "Cutting edge: TREM-2 attenuates macrophage activation" J Immunol 177(6):3520-4. PubMedThe triggering receptor expressed on myeloid cells 2 (TREM-2) delivers intracellular signals through the adaptor DAP12 to regulate myeloid cell function both within and outside the immune system. The role of TREM-2 in immunity has been obscured by the failure to detect expression of the TREM-2 protein in vivo. In this study, we show that TREM-2 is expressed on macrophages infiltrating the tissues from the circulation and that alternative activation with IL-4 can induce TREM-2. TREM-2 expression is abrogated by macrophage maturation with LPS of IFN-gamma. Using TREM-2(-/-) mice, we find that TREM-2 functions to inhibit cytokine production by macrophages in response to the TLR ligands LPS, zymosan, and CpG. Furthermore, we find that TREM-2 completely accounts for the increased cytokine production previously reported by DAP12(-/-) macrophages. Taken together, these data show that TREM-2 is expressed on newly differentiated and alternatively activated macrophages and functions to restrain macrophage activation.
