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Review Open Access

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

  • Authors:
    • Junqi Fan
    • Hongyan Shen
    • Dan Liu
    • Songbai Luo
    • Qingqing Huang
    • Yi Wen
    • Libang Yuan
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, The General Hospital of Western Theater Command, Chengdu, Sichuan 610083, P.R. China, Department of Rheumatology and Immunology, The General Hospital of Western Theater Command, Chengdu, Sichuan 610083, P.R. China, Department of Anesthesiology, The General Hospital of Western Theater Command, Chengdu, Sichuan 610083, P.R. China, Department of General Surgery, The General Hospital of Western Theater Command, Chengdu, Sichuan 610083, P.R. China
    Copyright: © Fan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 242
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    Published online on: July 2, 2026
       https://doi.org/10.3892/mmr.2026.13952
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Abstract

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.
View Figures

Figure 1

Functional heterogeneity and
context-dependent roles of TREM2+ microglia and
macrophages in the glioma microenvironment. Microenvironmental
stimuli induce diverse signaling pathways, including: i)
Immunosuppressive pathways, such as the JAK/STAT3 and NF-κB
pathways; and ii) immunoprotective processes, for example those
mediated by LYZ or CD163. These pathways shape CD4+ and
CD8+ T-cell responses and influence tumor progression.
Generated by Figdraw (https://www.figdraw.com/#/; copyright code:
YTOUT656f1). LYZ, lysozyme; TREM2, triggering receptor expressed on
myeloid cells 2; JAK, Janus kinase; M2, alternatively activated
macrophages.

Figure 2

Strategic roadmap for advancing
TREM2-targeted therapy in glioma. The diagram highlights three key
directions: i) Decoding spatial and functional heterogeneity of
TREM2 functions via single-cell and spatial transcriptomics; ii)
developing novel preclinical and therapeutic strategies, including
organoid models and nanotechnology; and iii) fostering
cross-disciplinary integration of clinical data through AI-driven
multi-omics and clinical translation. Generated by Figdraw
(https://www.figdraw.com/#/; copyright
code: SIYIT86e04). AI, artificial intelligence; TREM2, triggering
receptor expressed on myeloid cells 2.
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Copy and paste a formatted citation
Spandidos Publications style
Fan J, Shen H, Liu D, Luo S, Huang Q, Wen Y and Yuan L: TREM2 in glioma: Reprogramming the immune microenvironment from mechanistic understanding to clinical translation (Review). Mol Med Rep 34: 242, 2026.
APA
Fan, J., Shen, H., Liu, D., Luo, S., Huang, Q., Wen, Y., & Yuan, L. (2026). TREM2 in glioma: Reprogramming the immune microenvironment from mechanistic understanding to clinical translation (Review). Molecular Medicine Reports, 34, 242. https://doi.org/10.3892/mmr.2026.13952
MLA
Fan, J., Shen, H., Liu, D., Luo, S., Huang, Q., Wen, Y., Yuan, L."TREM2 in glioma: Reprogramming the immune microenvironment from mechanistic understanding to clinical translation (Review)". Molecular Medicine Reports 34.3 (2026): 242.
Chicago
Fan, J., Shen, H., Liu, D., Luo, S., Huang, Q., Wen, Y., Yuan, L."TREM2 in glioma: Reprogramming the immune microenvironment from mechanistic understanding to clinical translation (Review)". Molecular Medicine Reports 34, no. 3 (2026): 242. https://doi.org/10.3892/mmr.2026.13952
Copy and paste a formatted citation
x
Spandidos Publications style
Fan J, Shen H, Liu D, Luo S, Huang Q, Wen Y and Yuan L: TREM2 in glioma: Reprogramming the immune microenvironment from mechanistic understanding to clinical translation (Review). Mol Med Rep 34: 242, 2026.
APA
Fan, J., Shen, H., Liu, D., Luo, S., Huang, Q., Wen, Y., & Yuan, L. (2026). TREM2 in glioma: Reprogramming the immune microenvironment from mechanistic understanding to clinical translation (Review). Molecular Medicine Reports, 34, 242. https://doi.org/10.3892/mmr.2026.13952
MLA
Fan, J., Shen, H., Liu, D., Luo, S., Huang, Q., Wen, Y., Yuan, L."TREM2 in glioma: Reprogramming the immune microenvironment from mechanistic understanding to clinical translation (Review)". Molecular Medicine Reports 34.3 (2026): 242.
Chicago
Fan, J., Shen, H., Liu, D., Luo, S., Huang, Q., Wen, Y., Yuan, L."TREM2 in glioma: Reprogramming the immune microenvironment from mechanistic understanding to clinical translation (Review)". Molecular Medicine Reports 34, no. 3 (2026): 242. https://doi.org/10.3892/mmr.2026.13952
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