Objectives: T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a promising checkpoint. However, its features and prognostic value in lung adenocarcinoma remain undetermined. In this study, we aimed to characterize TIM-3 expression and its prognostic significance in patients with surgically resected lung adenocarcinoma.
Materials and methods: Expression of TIM-3 and programmed cell death 1 (PD-1), and density of CD8+ tumor infiltrating lymphocytes (TILs) were evaluated by immunohistochemistry in resected lung adenocarcinoma. The association between clinicopathological features or clinical outcomes and TIM-3 expression was analyzed.
Results: A total of 223 patients were enrolled. TIM-3 expression was observed in 107 (48.0%) samples. Positive TIM-3 expression significantly correlated with positive PD-1 expression (p < 0.001) and high CD8+ TILs density (p = 0.014). TIM-3 positivity was significantly associated with worse recurrence-free survival (RFS) (hazard ratio [HR], 2.32; 95% confidence interval [CI], 1.44-3.73, p = 0.001) and overall survival (OS) (HR, 2.04; 95% CI, 1.29-3.20, p = 0.002). Subgroup analysis revealed that TIM-3+/PD-1+/CD8 low group had the worst RFS (5-year rate: 39.5%, p = 0.002) and OS (5-year rate: 50.0%, p = 0.035), while TIM-3-/PD-1-/CD8 high group had the best RFS (5-year rate: 93.8%, p = 0.002) and OS (5-year rate: 100%, p = 0.035).
Conclusion: TIM-3 had a relatively high positive expression rate and special clinicopathological features in patients with lung adenocarcinoma. A combination of TIM-3 and/or PD-1 expression or CD8+ TILs density could further stratify patients into different groups with distinct prognosis.
Keywords: Immunotherapy; Lung adenocarcinoma; PD-1; TILs; TIM-3.
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