TREM2 is associated with tumor immunity and implies poor prognosis in glioma

Abstract

Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed in myeloid cells of the central nervous system (CNS), which mediate the immunological response in a variety of diseases. Uncertain is the function of TREM2 in glioma and tumor immune responses. In this research, the expression patterns of TREM2 in glioma were analyzed, along with its prognostic value and functional roles. TREM2 expression is increased in glioblastomas, gliomas with a mesenchymal subtype, gliomas with wild-type isocitrate dehydrogenase, and gliomas without 1p/19q deletion, all of which suggest the aggressiveness and poor prognosis of gliomas. Gene ontology, KEGG, and Gene set variation analyses indicated that TREM2 may serve as an immune response mediator. However, the function of T cells against tumor cells was negatively correlated with TREM2, suggesting that TREM2 may suppress tumor immunity. Further investigation demonstrated a correlation between TREM2 expression and immune checkpoint expression. CIBERSORT research revealed a link between a higher TREM2 expression level and the enrichment of tumor-associated macrophages, especially M2 subtype. Single-cell analysis and multiple immunohistochemical staining results showed that microglia and macrophage cells expressed TREM2. Immunofluorescent staining indicated that knocking down the expression of TREM2 would result in a decrease in M2 polarization. TREM2 was discovered to be an independent prognostic factor in glioma. In conclusion, our findings revealed that TREM2 was significantly expressed in microglia and macrophage cells and was intimately associated with the tumor immune microenvironment. Thus, it is expected that small-molecule medications targeting TREM2 or monoclonal antibodies would enhance the efficacy of glioma immunotherapy.

Keywords: TREM2; glioma; macrophage; prognosis; tumor immunity.