探讨Tim-3在非小细胞肺癌浸润巨噬细胞上的表达及其对预后的影响

背景与目的：T细胞免疫球蛋白和黏蛋白域分子3(T cell immunoglobulin and mucin-domaincontaining molecules 3，Tim-3)在免疫调节中起重要作用，参与多种疾病的发生、发展，且与疾病免疫逃逸和疾病临床预后明显相关。该研究旨在探讨负性共刺激分子Tim-3在非小细胞肺癌(non-small cell lung cancer，NSCLC)浸润巨噬细胞中的表达及临床意义。方法：采用免疫组织化学法检测126例NSCLC患者中Tim-3的表达水平，分析肿瘤组织浸润巨噬细胞Tim-3的表达水平与临床病理特征间的关系，并进一步分析Tim-3的表达水平对NSCLC患者预后的影响。结果：Tim-3主要分布于巨噬细胞的细胞质和细胞膜中；Tim-3在肿瘤浸润巨噬细胞中的表达水平与肿瘤大小、淋巴结转移及TNM分期均显著相关(P=0.002、0.045和0.022)；Tim-3在肿瘤浸润巨噬细胞中的表达水平可显著影响NSCLC患者的生存及预后，在Ⅲ期NSCLC患者中，Tim-3的表达越高，患者总生存期(overall survival，OS)越短(Ⅲ期：χ²=12.910，P=0.000，中位OS分别为80和32个月)。而且，Tim-3的表达水平与Ⅲ期NSCLC患者的无疾病生存期(disease free survival，DFS)也显著相关(χ²=6.135，P=0.013，中位DFS分别为41和24个月)，高表达Tim-3的NSCLC患者DFS短。另外，在Ⅲ期NSCLC患者中，Tim-3在淋巴细胞中的表达水平与OS和PFS呈负相关(χ²=4.737，P=0.030，中位OS分别为80和47个月；χ²=5.882，P=0.015，中位DFS分别为41和24个月)。结论：Tim-3在肿瘤免疫中起负性调节作用从而促进免疫逃逸，对患者的生存及预后有不良影响。

A study on the expression of Tim-3 in macrophages and its role in prognosis of non-small cell lung cancer

Background and purpose: T cell immunoglobulin and mucin-domain-containing molecules 3 (Tim-3) plays a pivotal role in immune regulation. It participates in the occurrence and development of a variety of diseases, and Tim-3 is associated with immune escape and poor prognosis. The aim of this study was to investigate the expression of negative costimulatory molecule, Tim-3, in macrophages in non-small cell lung cancer (NSCLC) and explore the clinical significance of the expression. Methods: A total of 126 human lung cancer tissue specimens were obtained from pathologically confirmed and newly diagnosed NSCLC patients. The expression level of Tim-3 was analyzed by immunohistochemistry staining. Correlation analysis was performed to study the relationship between Tim-3 expression in macrophagesand clinicopathological features. Survival analysis was performed by Kaplan-Meier. Results: Tim-3 was mainly expressed in the cytoplasm and cell membrane of macrophages. Tumor size, lymph node metastasis, TNM stage were significantly correlated with Tim-3 expression level (P=0.002, 0.045 and 0.022, respectively). Tim-3 expression in macrophages was negatively correlated with the prognosis of patients. Higher Tim-3 expression had a shorter overall survival (OS) in patients with stage Ⅲ NSCLC (χ²=12.910, P=0.000; Median OS: 80 months vs 32 months). Moreover, the expression level of Tim-3 had negative correlation with disease-free survival (DFS) in patients with stage Ⅲ NSCLC (χ²=6.135, P=0.013; Median DFS: 41 months vs 24 months). In addition, Tim-3 expression in lymphocytes was negatively correlated with OS and DFS in patients with stage Ⅲ NSCLC (χ²=4.737, P=0.030, Median OS: 80 months vs 47 months; χ²=5.882, P=0.015, Median DFS: 41 months vs 24 months). Conclusion: Tim-3, as a key negative regulator in anti-tumor immunity, contributes to the tumor immune evasion. It has an adverse influence on the prognosis of NSCLC patients.