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1. 天津医科大学肿瘤医院国家肿瘤临床医学研究中心,天津,300060
2. 天津市“肿瘤防治”重点实验室,天津,300060
3. 天津市恶性肿瘤临床医学研究中心,天津,300060
4. 天津市肿瘤免疫与生物治疗重点实验室,天津,300060
网络出版:2017-08-16,
纸质出版:2017-08-16
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申学杰,潘 娜,魏 枫,等. 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[J]. 中国癌症杂志, 2017, 27(7): 559-568.
申学杰, 潘 娜, 魏 枫. A study on the expression of Tim-3 in macrophages and its role in prognosis of non-small cell lung cancer[J]. China Oncology, 2017, 27(7): 559-568.
申学杰,潘 娜,魏 枫,等. 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[J]. 中国癌症杂志, 2017, 27(7): 559-568. DOI: 10.19401/j.cnki.1007-3639.2017.07.007.
申学杰, 潘 娜, 魏 枫. A study on the expression of Tim-3 in macrophages and its role in prognosis of non-small cell lung cancer[J]. China Oncology, 2017, 27(7): 559-568. DOI: 10.19401/j.cnki.1007-3639.2017.07.007.
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:χ
2
=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(χ
2
=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(χ
2
=4.737,P=0.030,中位OS分别为80和47个月;χ
2
=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。
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 costi
mulatory 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 macrophages and 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 (χ
2
=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 (χ
2
=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 (χ
2
=4.737
P=0.030
Median OS: 80 months vs 47 months; χ
2
=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.
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