Department of Thoracic Surgery, Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Ann Thorac Surg. 2020 May;109(5):1551-1557. doi: 10.1016/j.athoracsur.2019.12.017. Epub 2020 Jan 24.
T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a promising checkpoint. However, its features and prognostic value remain undetermined in esophageal squamous cell carcinoma (ESCC). This study evaluated the prognostic value of TIM-3 expression and its relationship with programmed cell death 1 (PD-1) and CD8 tumor-infiltrating lymphocytes (TILs) in patients with surgically resected ESCC.
Expression levels of TIM-3, PD-1, and CD8 TILs in ESCC were determined by immunohistochemistry. The association between clinicopathologic features or clinical outcomes and TIM-3 expression was analyzed.
A total of 183 patients with ESCC who had undergone esophagectomy without implementation of neoadjuvant therapy at the Second Affiliated Hospital of Soochow University in Suzhou, China from January 2009 to December 2014 were included. PD-1 positivity (P = .032) and high CD8 TIL density (P = .035) significantly correlated with positive TIM-3 expression. TIM-3 positivity was an independent risk factor for recurrence-free survival (RFS) (P < .001) and overall survival (OS) (P < .001). Subgroup analysis revealed that the TIM-3PD-1CD8 low group had the worst RFS and OS, whereas the TIM-3PD-1CD8 high group had the best RFS and OS (RFS: log-rank test P < .001; OS: log-rank test P < .001).
Positive TIM-3 expression was associated with PD-1 positivity and high CD8 TIL density and was an independent risk factor for RFS and OS in ESCC. Furthermore, the combination of TIM-3 and PD-1 expression or CD8 TIL density could further stratify patients into different groups with distinct prognosis.
T 细胞免疫球蛋白和粘蛋白结构域 3（TIM-3）是一种很有前途的检查点。然而，其在食管鳞状细胞癌（ESCC）中的特征和预后价值仍不确定。本研究评估了 TIM-3 表达在接受手术切除的 ESCC 患者中的预后价值及其与程序性细胞死亡蛋白 1（PD-1）和 CD8 肿瘤浸润淋巴细胞（TILs）的关系。
采用免疫组织化学法检测 ESCC 中 TIM-3、PD-1 和 CD8 TILs 的表达水平。分析 TIM-3 表达与临床病理特征或临床结局的关系。
共纳入苏州大学附属第二医院 2009 年 1 月至 2014 年 12 月期间未经新辅助治疗而行食管癌切除术的 183 例 ESCC 患者。PD-1 阳性（P=0.032）和高 CD8 TIL 密度（P=0.035）与 TIM-3 阳性表达显著相关。TIM-3 阳性是无复发生存（RFS）（P<0.001）和总生存（OS）（P<0.001）的独立危险因素。亚组分析显示，TIM-3PD-1CD8 低组的 RFS 和 OS 最差，而 TIM-3PD-1CD8 高组的 RFS 和 OS 最好（RFS：log-rank 检验 P<0.001；OS：log-rank 检验 P<0.001）。
TIM-3 阳性表达与 PD-1 阳性和高 CD8 TIL 密度相关，是 ESCC 患者 RFS 和 OS 的独立危险因素。此外，TIM-3 与 PD-1 表达或 CD8 TIL 密度的联合可进一步将患者分为不同预后的亚组。
