TREM2 Is Associated with Advanced Stages and Inferior Prognosis in Oral Squamous Cell Carcinoma

SIMPLE SUMMARY: Triggering receptor expressed on myeloid cells 2 (TREM2) is an appealing candidate for immunotherapy. However, results regarding its role in multiple cancers are rare or even contradictory. We showed that TREM2 expression in immune cells, among which were macrophages in peripheral blood mononuclear cells and tumor-associated macrophages, was associated with advanced tumor stages and reduced survival rates in oral squamous cell carcinoma (OSCC) patients. Our findings implicate that TREM2 could serve as an effective target for prognostic and therapeutic approaches in OSCC patients. Anti-TREM2 immunotherapy might greatly improve patients’ prognosis. High levels of sTREM2 were associated with advanced UICC stages, indicating that sTREM2 might be a biomarker in OSCC patients. ABSTRACT: Triggering receptor expressed on myeloid cells 2 (TREM2) is suggested to hamper antitumor immune response in multiple cancers. However, the role of TREM2 in oral squamous cell carcinoma (OSCC) and its expression in tumor-associated macrophages (TAMs) are unknown. In this study, TREM2 expression was analyzed in the primary tumors and corresponding lymph-node metastases of OSCC patients via immunohistochemistry on tissue microarrays. Human peripheral blood mononuclear cells (PBMCs) and single-cell suspensions of tumor and healthy adjacent tissues were analyzed for the presence of TREM2(+) macrophages and TAMs using flow cytometry. The serum levels of soluble TREM2 (sTREM2) were quantified using an enzyme-linked immunosorbent assay. High TREM2 expression was associated with advanced UICC stages (Spearman’s rank correlation (SRC), p = 0.04) and significantly reduced survival rates in primary tumors (multivariate Cox regression, progression-free survival: hazard ratio (HR) of 2.548, 95% confidence interval (CI) of 1.089–5.964, p = 0.028; overall survival: HR of 2.17, 95% CI of 1.021–4.613, p = 0.044). TREM2 expression was significantly increased in the PBMCs of OSCC patients in UICC stage IV compared with healthy controls (ANOVA, p < 0.05). The serum levels of sTREM2 were higher in advanced UICC stages, but they narrowly missed significance (SRC, p = 0.059). We demonstrated that TREM2 was multi-factorially associated with advanced stages and inferior prognosis in OSCC patients and that it could serve as a prognostic biomarker in OSCC patients. Targeting TREM2 has the potential to reshape the local and systemic immune landscape for the potential enhancement of patients’ prognosis.