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非小细胞肺癌中的T细胞免疫球蛋白和粘蛋白结构域包含分子3

T cell immunoglobulin and mucin-domain containing-3 in non-small cell lung cancer.

作者信息

Jia Keyi, He Yayi, Dziadziuszko Rafal, Zhao Sha, Zhang Xiaoshen, Deng Juan, Wang Hao, Hirsch Fred R, Zhou Caicun, Yu Hui, Zhang Liping

机构信息

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai 200433, China.

School of Medicine, Tongji University, Shanghai 200433, China.

出版信息

Transl Lung Cancer Res. 2019 Dec;8(6):895-906. doi: 10.21037/tlcr.2019.11.17.

Abstract

BACKGROUND

Immunotherapy has shown promising effect for non-small cell lung cancer (NSCLC) patients. Yet the biomarkers for predicting immunotherapy efficiency are still lacking.

METHODS

We tested 139 surgical resected NSCLC primary tumor samples from Medical University of Gdansk, Poland, for T cell immunoglobulin and mucin-domain containing-3 (TIM-3) level by immunohistochemistry (IHC), analyzed the expression of TIM-3 protein on NSCLC tumor cells and tumor infiltrating lymphocytes (TILs).

RESULTS

TIM-3 on TILs was correlated with programmed cell death protein-1 (PD-1) on TILs (correlation coefficient =0.346, P<0.001) and programmed cell death protein-ligand 1 (PD-L1) on TILs (correlation coefficient =0.313, P<0.001), PD-L1 level on tumor cells (correlation coefficient =0.255, P=0.002), TIM-3 level on tumor cells (correlation coefficient =0.262, P=0.002) and TIL percentage (correlation coefficient =0.172, P=0.043). TIM-3 level on tumor cells only had correlation with PD-L1 level (correlation coefficient =0.170, P=0.045). High level of TIM-3 on TILs indicated shorter recurrence-free survival (RFS) and overall survival (OS) (RFS 1.800 years, 95% CI, 1.230-2.370 0.870 years, 95% CI, 0.212-1.528, P=0.048) (OS 2.960 years, 95% CI, 2.268-3.652 1.080 years, 95% CI, 0.228-1.932, P=0.034).

CONCLUSIONS

TIM-3 is expressed on NSCLC tumor cells and TILs in all NSCLC pathological type. TIM-3 level on TILs had correlation with PD-1 and PD-L1 level. NSCLC patients with high TIM-3 level on TILs were more likely to have poor prognosis.

摘要

背景

免疫疗法已在非小细胞肺癌(NSCLC)患者中显示出有前景的疗效。然而,仍缺乏预测免疫疗法疗效的生物标志物。

方法

我们通过免疫组织化学(IHC)检测了来自波兰格但斯克医科大学的139例手术切除的NSCLC原发性肿瘤样本中的T细胞免疫球蛋白和粘蛋白结构域包含分子3(TIM-3)水平,分析了TIM-3蛋白在NSCLC肿瘤细胞和肿瘤浸润淋巴细胞(TILs)上的表达。

结果

TILs上的TIM-3与TILs上的程序性细胞死亡蛋白1(PD-1)(相关系数=0.346,P<0.001)、TILs上的程序性细胞死亡蛋白配体1(PD-L1)(相关系数=0.313,P<0.001)、肿瘤细胞上的PD-L1水平(相关系数=0.255,P=0.002)、肿瘤细胞上的TIM-3水平(相关系数=0.262,P=0.002)以及TIL百分比(相关系数=0.172,P=0.043)相关。肿瘤细胞上的TIM-3水平仅与PD-L1水平相关(相关系数=0.170,P=0.045)。TILs上TIM-3水平高表明无复发生存期(RFS)和总生存期(OS)较短(RFS 1.800年,95%CI,1.230 - 2.370对0.870年,95%CI,0.212 - 1.528,P=0.048)(OS 2.960年,95%CI,2.268 - 3.652对1.080年,95%CI,0.228 - 1.932,P=0.034)。

结论

TIM-3在所有NSCLC病理类型的肿瘤细胞和TILs上均有表达。TILs上的TIM-3水平与PD-1和PD-L1水平相关。TILs上TIM-3水平高的NSCLC患者预后更差。

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