Triggering receptor expressed on myeloid cells 2 (TREM2) (TREM2)

Triggering receptor expressed on myeloid cells 2 (TREM2) is a single-pass transmembrane receptor primarily expressed on microglia in the central nervous system and on various peripheral myeloid cells, such as macrophages and dendritic cells [1, 3]. It functions as a critical sensor for lipids, lipoproteins, and amyloid-beta, signaling through the adapter protein DAP12 to regulate cell survival, proliferation, and phagocytic activity [3, 5]. In neurodegenerative conditions like Alzheimer's disease, TREM2 is essential for the microglial response to protein aggregates; genetic variants that impair its function significantly increase disease risk [2]. In the field of oncology, TREM2 is often upregulated on tumor-associated macrophages (TAMs), where it promotes an immunosuppressive environment that hinders anti-tumor immunity [3]. Therapeutic development focuses on agonistic antibodies to boost TREM2 activity in Alzheimer's disease and antagonistic antibodies to modulate the immune landscape in cancer [4].

Other names

TREM-2Triggering receptor expressed on monocytes 2

Agonism of the TREM2 receptor to enhance microglial clearance of amyloid-beta and promote cell survival; Antagonism of TREM2 to deplete tumor-associated macrophages [3, 4].