Increased TIM-3 expression in tumor-associated macrophages predicts a poorer prognosis in non-small cell lung cancer: a retrospective cohort study

Abstract

Background: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is considered a key negative regulator in T-cell-mediated response. However, few studies have been reported on the relationship between TIM-3 expression in tumor-associated macrophages (TAMs) and clinicopathological characteristics of patients. This study evaluated the correlation between the expression of TIM-3 on the surface of TAMs macrophages in tumor matrix and the clinical outcome of patients with non-small cell lung cancer (NSCLC). Methods: The expression of CD68, CD163 and TIM-3 in 248 NSCLC patients who underwent surgery in Zhoushan Hospital from January 2010 to January 2013 was detected by immunohistochemistry (IHC). From the date of operation to the date of death, overall survival (OS) was measured to analyze the relationship between the expression of Tim-3 and the prognosis of NSCLC patients. Results: The study assessed 248 patients with NSCLC. TIM-3 expression in TAMs was more frequently identified in patients with higher carcinoembryonic antigen (CEA) levels, lymph node metastasis, higher grade, high CD68 expression, and high CD163 expression (P<0.05). The OS of the high TIM-3 expression groups was shorter than that of the low TIM-3 expression groups (P=0.01). Patients with high TIM-3 and CD68/CD163 expressions had the worst prognosis, whereas patients with low expressions of both TIM-3 and CD68/CD163 had the best prognosis (P<0.05). In NSCLC, the OS of the high TIM-3 expression groups was shorter than that of the low TIM-3 expression groups (P=0.01). In lung adenocarcinoma, the OS of the high TIM-3 expression groups was shorter than that of the low TIM-3 expression groups(P=0.03). Conclusions: TIM-3 expression in TAMs may be a promising prognostic biomarker for NSCLC or adenocarcinoma. Our results demonstrated that high TIM-3 expression in TAMs was an independent predictor of worse prognosis in patients.