TREM2 in glioma: Reprogramming the immune microenvironment from mechanistic understanding to clinical translation (Review)

The poor prognosis of high‑grade gliomas, such as glioblastoma, is largely driven by a notably immunosuppressive tumor microenvironment (TME), wherein microglia and tumor‑associated macrophages play important roles. The present review summarizes the current evidence supporting triggering receptor expressed on myeloid cells 2 (TREM2) as a key immunoregulator in the glioma TME. The present review explores the context‑dependent dual role of TREM2, which can either be hijacked to promote immunosuppression and tumor progression or inhibit tumor progression through its notable functions in phagocytosis and antigen presentation. The present review also examines the clinical association of TREM2 expression with glioma grade and patient prognosis, evaluating its potential as a diagnostic and prognostic biomarker. Furthermore, the present review discusses the current landscape of TREM2‑targeted therapeutic strategies, from direct TREM2 inhibition and myeloid‑targeted immunocytokines to nano‑engineered drug delivery systems, and addresses the core translational challenges of these strategies. Looking forward, the importance of leveraging spatial multi‑omics and artificial intelligence to decipher the functional heterogeneity of TREM2 and to guide precision immunotherapy is highlighted. In conclusion, the present review provides a comprehensive framework for understanding the role of TREM2 in glioma; this receptor serves not only as a biomarker for glioma, but as an important signaling hub in the glioma TME. Therefore, the present review aims to support the development of novel therapeutic strategies targeting the immune microenvironment in glioma.