TREM2: friend or foe in glioma?

Triggering receptor expressed on myeloid cells 2 (TREM2) is a neuroimmune signaling hub involved in key cellular processes including microglial phagocytosis, chemotaxis, and inflammation. Dysregulation of TREM2 has been implicated in a variety of diseases, most notably in the innate immune response to neurodegenerative disorders and cancer. The TREM2 pathway plays a significant role in governing microglia phenotypic transitions in Alzheimer's disease, as well as in regulating tumor-associated macrophages' ability to modulate cytotoxic activity. However, TREM2's role can be dependent on experimental parameters and disease contexts. Due to its intricate involvement in related disorders and the myeloid-dominated microenvironment in brain tumors, TREM2 has emerged as a vital player to better understand neuroimmune contributions to central nervous system malignancies. This review critically evaluates TREM2's controversial function in gliomas, analyzes experimental and biological variables that may underlie divergent findings, and outlines important considerations for future investigations.