Significance Of TIM-3 Expression In Esophageal Squamous Cell Carcinoma

Objective:The features and prognostic value of T-cell immunoglobulin and mucin-domain containing-3(TIM-3),programmed cell death 1(PD-1)and tumor-infiltrating lymphocytes(TILs)remain undetermined in esophageal squamous cell carcinoma(ESCC).In this study,we assessed the expression of TIM-3 in patients with surgically resected ESCC,and we also evaluated its association with PD-1 and CD8+TILs.Methods:A retrospective analysis was performed on 261 patients who underwent thoracic surgery for esophageal carcinoma in our department.Expression of TIM-3,PD-1 and CD8+TILs in ESCC were determined by immunohistochemistry.The relationship between clinical data and TIM-3 expression was performed by a logistic regression model.Prognostic factors were analyzed using a Cox regression model.Results:183 patients with ESCC who had undergone thoracic surgery were included.87(47.5%)cases were classified as TIM-3 positive.PD-1 positivity(p=0.032)and high CD8+TILs density(p=0.035)significantly correlated with positive TIM-3 expression.TIM-3 positivity was an risk factor for recurrence-free survival(RFS)(p<0.001)and overall survival(OS)(p<0.001).Subgroup analysis revealed that TIM-3+PD-1+CD8 low group had the worst RFS and OS,whereas TIM-3-PD-CD8 high group had the best RFS and OS(RFS:Log-rank test p<0.001;OS:Log-rank test p<0.001)?Conclusions:Positive TIM-3 expression was associated with PD-1 positivity and high CD8+TILs density,which was an independent risk factor for RFS and OS in ESCC.Furthermore,the combination of TIM-3 and/or PD-1 expression or CD8+TILs density could further stratify patients into different groups with distinct prognosis.