TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression.
TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression.
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TIM-3 表达是肿瘤组织中调节性 T 细胞的特征，并与肺癌进展相关
DOI：
10.1371/journal.pone.0030676
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lu B
中科院分区：
文献类型：
--
作者：
Gao X;Zhu Y;Li G;Huang H;Zhang G;Wang F;Sun J;Yang Q;Zhang X;Lu B
背景T细胞免疫球蛋白-3(TIM-3)是一种负性调节分子，在免疫耐受中起重要作用。在慢性感染和肿瘤中，TIM-3在耗尽的CD8+T细胞中表达上调。然而，肿瘤微环境中TIM-3+CD4+T细胞的性质尚不清楚。本研究旨在研究人肺癌组织中表达TIM-3的淋巴细胞的特征，探讨TIM-3在肺癌进展中的临床意义。方法收集51例经病理证实和新诊断的非小细胞肺癌(NSCLC)患者的肺癌组织标本。用流式细胞仪分析肿瘤组织、远端正常肺组织和外周血单核细胞(PBMC)中的白细胞表面TIM-3的表达。肿瘤浸润性淋巴细胞(TIL)上TIM-3的表达与临床病理参数相关。结论TIM-3在人肺癌组织的CD4+和CD8+TIL上均高度上调，而在患者外周血T细胞上的表达很低。TIM-3+γ+TIL与TIM-3−CD8+TIL相比，TIM-3+CD8+TIL的干扰素-CD8+细胞频率降低。然而，CD8+TIL上TIM-3的表达水平与临床病理参数无关。有趣的是，我们发现大约70%的TIM-3+CD4+TIL表达FOXP3，大约60%的FOXP3+TIL表达TIM-3+。重要的是，TIM-3在CD4+T细胞上的表达与NSCLC不良的临床病理参数相关，如淋巴结转移和晚期癌症分期。我们的研究揭示了TIM-3通过其在调节性T细胞中的优势表达而在肿瘤微环境中作为重要的免疫调节因子的新作用。
Background T cell immunoglobulin-3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in immune tolerance. TIM-3 is upregulated in exhausted CD8+ T cells in both chronic infection and tumor. However, the nature of TIM-3+CD4+ T cells in the tumor microenvironment is unclear. This study is to characterize TIM-3 expressing lymphocytes within human lung cancer tissues and establish clinical significance of TIM-3 expression in lung cancer progression. Methodology A total of 51 human lung cancer tissue specimens were obtained from pathologically confirmed and newly diagnosed non-small cell lung cancer (NSCLC) patients. Leukocytes from tumor tissues, distal normal lung tissues, and peripheral blood mononuclear cells (PBMC) were analyzed for TIM-3 surface expression by flow cytometry. TIM-3 expression on tumor-infiltrating lymphocytes (TILs) was correlated with clinicopathological parameters. Conclusions TIM-3 is highly upregulated on both CD4+ and CD8+ TILs from human lung cancer tissues but negligibly expressed on T cells from patients' peripheral blood. Frequencies of IFN-γ+ cells were reduced in TIM-3+CD8+ TILs compared to TIM-3−CD8+ TILs. However, the level of TIM-3 expression on CD8+ TILs failed to associate with any clinical pathological parameter. Interestingly, we found that approximately 70% of TIM-3+CD4+ TILs expressed FOXP3 and about 60% of FOXP3+ TILs were TIM-3+. Importantly, TIM-3 expression on CD4+ T cells correlated with poor clinicopathological parameters of NSCLC such as nodal metastasis and advanced cancer stages. Our study reveals a new role of TIM-3 as an important immune regulator in the tumor microenvironment via its predominant expression in regulatory T cells.
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DOI：
10.4049/jimmunol.0903435
发表时间：
2010-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Boenisch O;D'Addio F;Watanabe T;Elyaman W;Magee CN;Yeung MY;Padera RF;Rodig SJ;Murayama T;Tanaka K;Yuan X;Ueno T;Jurisch A;Mfarrej B;Akiba H;Yagita H;Najafian N
通讯作者：
Najafian N
影响因子：
30.5
作者：
Sabatos, CA;Chakravarti, S;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.1084/jem.20100643
发表时间：
2010-09-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Sakuishi K;Apetoh L;Sullivan JM;Blazar BR;Kuchroo VK;Anderson AC
通讯作者：
Anderson AC
影响因子：
64.8
作者：
Monney, L;Sabatos, CA;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.1084/jem.20081398
发表时间：
2008-11-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jones RB;Ndhlovu LC;Barbour JD;Sheth PM;Jha AR;Long BR;Wong JC;Satkunarajah M;Schweneker M;Chapman JM;Gyenes G;Vali B;Hyrcza MD;Yue FY;Kovacs C;Sassi A;Loutfy M;Halpenny R;Persad D;Spotts G;Hecht FM;Chun TW;McCune JM;Kaul R;Rini JM;Nixon DF;Ostrowski MA
通讯作者：
Ostrowski MA