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

doi:10.19401/j.cnki.1007-3639.2017.07.007

中国癌症杂志 ›› 2017, Vol. 27 ›› Issue (7): 559-568.doi: 10.19401/j.cnki.1007-3639.2017.07.007

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

申学杰^1,2,3,4，潘　娜^1,2,3,4，魏　枫^1,2,3,4，王　扬^1,2,3,4，郑　禹^1,2,3,4，金　昊^1,2,3,4，曹　水^1,2,3,4，任秀宝^1,2,3,4

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

出版日期:2017-07-30 发布日期:2017-08-16
通信作者: 曹　水　E-mail: caoshui9999@163.com
基金资助:
国家科技支撑计划(2015BAI12B00)；国家自然科学基金(81272221)。

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

SHEN Xuejie^1,2,3,4, PAN Na^1,2,3,4, WEI Feng^1,2,3,4, WANG Yang^1,2,3,4, ZHENG Yu^1,2,3,4, JIN Hao^1,2,3,4, CAO Shui^1,2,3,4, REN Xiubao^1,2,3,4

1. National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; 2. Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China; 3. Tianjin Clinical Research Center for Cancer, Tianjin 300060, China; 4. Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China

Published:2017-07-30 Online:2017-08-16
Contact: CAO Shui E-mail: caoshui9999@163.com

摘要/Abstract

摘要： 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。

关键词: T细胞免疫球蛋白和黏蛋白域分子3, 非小细胞肺癌, 巨噬细胞, 预后

Abstract: 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 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 (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.

Key words: T cell immunoglobulin and mucin-domain-containing molecules 3, Non-small cell lung carcinoma, Macrophages, Prognosis

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.

SHEN Xuejie, PAN Na, WEI Feng, et al. 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.

[1]	林艺, 王策, 康勋, 康庄, 陈峰, 江波, 李文斌. 胶质母细胞瘤复发相关基因的筛选、表达和临床预后分析[J]. 中国癌症杂志, 2022, 32(1): 13-23.
[2]	马祎菲, 梁新军, 魏少忠 . 炎症与免疫指标在可切除性结直肠癌中的预后价值[J]. 中国癌症杂志, 2021, 31(9): 845-851.
[3]	雷雅洁, 高　毅, 王治洁, 程　玺, 杨雨菲, 周宏宇, 陈丽华, 陈伊新, 李浩然, 李子庭, 吴小华 . 早期卵巢癌（Ⅰ C ~ⅡA）患者腹主动脉旁淋巴结清扫术对预后影响的临床分析[J]. 中国癌症杂志, 2021, 31(8): 740-745.
[4]	朱逸晖, 李　婷, 胡夕春. Trastuzumab deruxtecan的临床研究进展及展望——HER2耐药患者的新希望[J]. 中国癌症杂志, 2021, 31(8): 754-761.
[5]	高鹤丽, 徐　近, 虞先濬. 分化好的胃肠胰神经内分泌瘤G3的诊治新进展[J]. 中国癌症杂志, 2021, 31(7): 567-573.
[6]	李海洲, 张艳炜, 许英杰, 杨　门, 张　磊, 韩京军 . miR-933调控KLF6基因影响非小细胞肺癌的作用研究[J]. 中国癌症杂志, 2021, 31(7): 581-588.
[7]	杨　佳, 刘舒媛, 王莹莹, 李盈甫, 马千里, 李　玙, 王永蓉, 李传印, 谭　芳 . 云南省汉族人群TNF-α基因多态性与非小细胞肺癌发生、发展的相关性[J]. 中国癌症杂志, 2021, 31(7): 616-628.
[8]	巩润泽, 胡海燕. CCL2在骨肉瘤组织中的表达及其临床意义[J]. 中国癌症杂志, 2021, 31(6): 455-459.
[9]	郑培明, 李俊蒙, 张　鹏, 高　岚 . 巨噬细胞外泌体源miR-223促进胃癌细胞对奥沙利铂的耐药研究[J]. 中国癌症杂志, 2021, 31(5): 368-378.
[10]	彭子珊, 孔　辉, 鲍　真, 赵红杏, 刘　鑫, 卢韶华. 83例多发肺腺癌患者的临床病理学特征分析[J]. 中国癌症杂志, 2021, 31(5): 408-418.
[11]	肖　锋, 肖静文, 邵建国, 陈丽燕, 顾春燕 . PD-1在肝细胞癌肿瘤浸润淋巴细胞中的表达及与预后的相关性[J]. 中国癌症杂志, 2021, 31(5): 419-427.
[12]	王春建 , 聂　刚 , 毛　艳 . TRIP6在乳腺癌中的作用及其机制研究[J]. 中国癌症杂志, 2021, 31(3): 161-169.
[13]	义维丽, 赵文成, 黄东宁, 覃　莉, 吴新天, 周　斐, 吴凤英 . PD-1单抗治疗非小细胞肺癌相关不良反应及其与疗效的相关性分析[J]. 中国癌症杂志, 2021, 31(3): 203-211.
[14]	武元元 , 王　军 , 刘勤江 , 张　明 . 甲状腺未分化癌的预后因素分析及治疗决策[J]. 中国癌症杂志, 2021, 31(3): 212-220.
[15]	杨柳松, 祝迎锋, 唐剑敏 . 上皮样胶质母细胞瘤10例报告并文献复习[J]. 中国癌症杂志, 2021, 31(2): 114-120.

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

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

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价