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[CD4⁺肿瘤浸润淋巴细胞上TIM-3的上调预示人类非小细胞肺癌预后不良]

[Up-regulation of TIM-3 on CD4+ tumor infiltrating lymphocytes predicts poor prognosis in human non-small-cell lung cancer].

作者信息

Ji Peng, Chen Dikang, Bian Jianye, Xia Rui, Song Xinyu, Wen Wen, Zhang Xueguang, Zhu Yibei

机构信息

School of Biology & Basic Medical Sciences, Soochow University, Suzhou 215123, China.

出版信息

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2015 Jun;31(6):808-11.

PMID:26062425
Abstract

OBJECTIVE

To characterize the expression of negative costimulatory molecule, T cell immunoglobulin and mucin-domain-containing molecules 3 (TIM-3), on tumor infiltrating lymphocytes (TILs) in human non-small-cell lung cancer (NSCLC) and explore the clinical significance of the expression.

METHODS

A total of 56 human lung cancer tissue specimens were obtained from pathologically confirmed and newly diagnosed NSCLC patients. Infiltrating lymphocytes from both tumor tissues and adjacent normal lung tissues were analyzed for TIM-3 expression by immunofluorescence staining and flow cytometry. Correlation analysis was performed between TIM-3 expression on TILs and the prognosis of the patients.

RESULTS

The expression of TIM-3 on CD4+ TILs in tumor tissues [(28.64±10.46)%] was significantly higher than that on CD4+ T cells in adjacent normal tissues [(13.32±6.95)%]. Similarly, the expression of TIM-3 on CD8+ TILs in tumor tissues [(30.77±15.58)%] was up-regulated as compared with that on CD8+ T cells in adjacent normal tissues [(12.98±8.19)%]. Moreover, majority of the TIM-3 positive TILs from both adjacent normal tissues and tumor lung tissues were positive for another negative costimulatory molecule, programmed death 1 (PD-1). Importantly, TIM-3 expression on CD4+ TILs was correlated with poor prognosis of the patients.

CONCLUSION

TIM-3, as a key negative regulator in the anti-tumor immunity, contributes to the tumor immune evasion. It has an adverse influence on the prognosis of NSCLC patients.

摘要

目的

表征负性共刺激分子T细胞免疫球蛋白黏蛋白结构域分子3(TIM-3)在人非小细胞肺癌(NSCLC)肿瘤浸润淋巴细胞(TILs)中的表达,并探讨该表达的临床意义。

方法

从经病理确诊的新诊断NSCLC患者中获取56例人肺癌组织标本。通过免疫荧光染色和流式细胞术分析肿瘤组织及相邻正常肺组织中的浸润淋巴细胞的TIM-3表达。对TILs上TIM-3表达与患者预后进行相关性分析。

结果

肿瘤组织中CD4⁺TILs上TIM-3的表达[(28.64±10.46)%]显著高于相邻正常组织中CD4⁺T细胞上的表达[(13.32±6.95)%]。同样,肿瘤组织中CD8⁺TILs上TIM-3的表达[(30.77±15.58)%]较相邻正常组织中CD8⁺T细胞上的表达[(12.98±8.19)%]上调。此外,来自相邻正常组织和肿瘤肺组织的大多数TIM-3阳性TILs对另一种负性共刺激分子程序性死亡蛋白1(PD-1)呈阳性。重要的是,CD4⁺TILs上的TIM-3表达与患者的不良预后相关。

结论

TIM-3作为抗肿瘤免疫中的关键负调节因子,有助于肿瘤免疫逃逸。它对NSCLC患者的预后有不良影响。

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