非小细胞肺癌患者外周血CD8+和γδT细胞亚群表面PD1和BTLA的表达

doi:10.24920/003498

摘要/Abstract

摘要： 目的探讨非小细胞肺癌（non-small cell lung cancer,NSCLC）患者外周血中程序性细胞死亡蛋白1（PD1）,B淋巴细胞和T淋巴细胞衰减因子（BTLA）的表达和调控;检测非小细胞肺癌中PD1和BTLA在mRNA水平的相关性。方法采用流式细胞分析术检测32例Ⅳ期NSCLC患者和30例健康人外周血CD8⁺和γδ⁺T细胞表面PD1和BTLA的表达。比较肺癌骨转移患者唑来膦酸治疗前后外周血γδ⁺T细胞表面PD1和BTLA的表达。使用cBioPortal数据平台采用Pearson相关性分析法分析PD1和BTLA及其配体之间的相关性。结果健康对照组（t=2.324,P=0.024）和NSCLC患者（t=2.498,P=0.015）外周血CD8⁺ T细胞表面PD1的频率显著高于γδT细胞。与健康对照组相比,晚期NSCLC患者CD8⁺ T细胞上PD1表达频率显著上调（t=4.829,P<0.001）,而γδ⁺ T细胞上PD1表达无显著差异。健康对照组外周血的PD1⁺BTLA⁺γδT细胞明显低于NSCLC患者（t=2.422,P=0.0185）。7例骨转移NSCLC患者唑来膦酸治疗前后PD1⁺γδ⁺和BTLA⁺γδ⁺ T细胞的频率未见明显差异。PD1的mRNA水平在肺腺癌（r=0.54,P<0.05）和肺鳞癌（r=0.78,P<0.05）患者均与BTLA的mRNA水平呈正相关。结论协同抑制分子在晚期NSCLC的CD8⁺ T细胞和γδT细胞表面均有上调,提示这些分子参与调控CD8⁺ T细胞和γδ⁺ T细胞的失活、免疫逃逸和肿瘤侵袭。

关键词: CD8⁺ T细胞, γδ T细胞;, 程序性死亡因子1（PD1）, B和T淋巴细胞衰减因子（BTLA）, 非小细胞肺癌

Abstract: Objective To investigate the expression and regulation of programmed cell death protein 1 (PD1), B lymphocyte and T lymphocyte attenuator (BTLA) in peripheral blood of patients with non-small cell lung cancer (NSCLC); to examine the correlation of the mRNA levels between PD and BTLA in NSCLC. Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8⁺T cells and γδ⁺ T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals. We compared the expression of PD1 and BTLA on the surfaces of γδ⁺ T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid. The correlations of PD1 and BTLA, as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform. Results The frequency of PD1 on the surfaces of CD8⁺ T cells was significantly higher than that of the γδT cells in both healthy controls (t=2.324, P=0.024) and NSCLC patients（t=2.498, P=0.015). The frequency of PD1 on CD8⁺ T cells, rather than on γδ⁺ T cells, was significantly upregulated in advanced NSCLC patients compared with that in healthy controls (t=4.829, P<0.001). The PD1⁺BTLA⁺γδT cells of the healthy controls were significantly lower than that of the NSCLC patients (t=2.422, P=0.0185). No differences in percentage of PD1⁺γδ⁺ and BTLA⁺γδ⁺ T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment. PD1 was positively correlated with BTLA in both lung adenocarcinoma (r=0.54; P<0.05) and lung squamous cell carcinoma (r=0.78; P<0.05). Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8⁺ T cells and γδT cells in advanced NSCLC, suggesting that these molecules were involved in regulating the inactivation of CD8⁺ T cells and γδ⁺ T cells, immune escape and tumor invasion.

Key words: CD8⁺ T cell, γδ T cell;, programmed cell death protein 1, B and T lymphocyte attenuator, non-small cell lung cancer

基金资助: 浙江省医药卫生科技计划(2016KYB292);嘉兴市科技计划项目(2016AY23054)

Bao Yi, Mo Juanfen, Wu Jiayuan, Cao Chenxi. Expression of PD1 and BTLA on the CD8⁺ T Cell and γδT Cell Subsets in Peripheral Blood of Non-Small Cell Lung Cancer Patients[J].Chinese Medical Sciences Journal, 2019, 34(4): 248-255.

图/表 5

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