[1]苏艳丽,李 波.Th9细胞对非小细胞肺癌患者CD8+T细胞抗肿瘤活性的调控作用[J].陕西医学杂志,2021,50(1):15-21.[doi:DOI:10.3969/j.issn.1000-7377.2021.01.004]
　SU Yanli,LI Bo.Regulatory of Th9 cells on anti-tumor activity of CD8+T cells in patients with non-small-cell lung cancer[J].,2021,50(1):15-21.[doi:DOI:10.3969/j.issn.1000-7377.2021.01.004]
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Th9细胞对非小细胞肺癌患者CD8+T细胞抗肿瘤活性的调控作用
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
50
期数:
2021年1期
页码:
15-21
栏目:
基础研究
出版日期:
2021-01-05

文章信息/Info

Title:
Regulatory of Th9 cells on anti-tumor activity of CD8+T cells in patients with non-small-cell lung cancer
作者:
苏艳丽; 李 波
(湖北省枣阳市第一人民医院呼吸与危重症医学科,湖北 枣阳 441200)
Author(s):
SU Yanli; LI Bo
(Department of Respiratory and Critical Care Medicine,the First People's Hospital of Zaoyang,Zaoyang 441200,China)
关键词:
非小细胞肺癌;  Th9细胞;  白细胞介素-9;  CD8阳性T淋巴细胞;  抗肿瘤
Keywords:
Non-small-cell lung cancer;  T helper 9 cells;  Interleukin-9;  CD8-positive T-lymphocytes;  Anti-tumour
分类号:
R 734.2
DOI:
DOI:10.3969/j.issn.1000-7377.2021.01.004
文献标志码:
A
摘要:
目的:观察并分析Th9细胞及其分泌的白细胞介素-9(IL-9)对非小细胞肺癌(NSCLC)患者CD8+T细胞抗肿瘤活性的影响。方法:选择32例NSCLC患者(肺癌组)和11例健康对照者(对照组)。分离肺癌组血浆、外周血单个核细胞(PBMCs)、肿瘤部位和非肿瘤部位的支气管肺泡灌洗液(BALF)及对照组血浆和PBMCs,检测Th9细胞比例、IL-9水平和转录因子PU.1 mRNA相对表达量。纯化肺癌组Th9细胞、CD8+T细胞和原代NSCLC细胞,使用重组IL-9刺激CD8+T细胞,观察细胞增殖和分泌穿孔素、颗粒酶B水平。建立Th9细胞、CD8+T细胞与原代NSCLC细胞的共培养细胞,观察IL-9对CD8+T细胞的细胞杀伤功能和非细胞杀伤功能的影响。组间比较采用t检验、配对t检验或Wilcoxon配对检验。结果:肺癌组外周血Th9细胞比例、IL-9水平和PU.1 mRNA相对表达量低于对照组(均P<0.0001),肺癌组肿瘤部位分离的BALF中Th9细胞比例、IL-9水平和PU.1 mRNA相对表达量低于非肿瘤部位(均P<0.0001)。IL-9刺激可增加肺癌组CD8+T细胞增殖和穿孔素、颗粒酶B分泌,IL-9刺激还可提升肺癌组CD8+T细胞对原代NSCLC细胞的细胞杀伤和非细胞杀伤功能,主要表现为细胞死亡比率增加、干扰素-γ和肿瘤坏死因子-α(TNF-α)分泌升高。Th9细胞也可提升肺癌组CD8+T细胞对原代NSCLC细胞的细胞杀伤和非细胞杀伤功能,抗IL-9中和抗体可抑制Th9细胞对CD8+T细胞功能的调控作用。结论:Th9细胞可能通过分泌IL-9在体外增强NSCLC患者CD8+T细胞的抗肿瘤功能。
Abstract:
Objective:To investigate the effect of Th9 cells and interleukin-9(IL-9)on anti-tumor activity of CD8+T cells in patients with non-small-cell lung cancer(NSCLC).Methods:32 NSCLC patients(NSCLC group)and 11 healthy persons(control group)were selected.Plasma,peripheral blood mononuclear cells(PBMCs),and bronchoalveolar lavage fluid(BALF)(both tumor site and non-tumor site)were collected from NSCLC group,while plasma and PBMCs were collected from control group.Percentage of Th9 cells,IL-9 level,and transcription factor PU.1 mRNA relative level were measured.Th9 cells,CD8+T cells,and primary NSCLC cells were purified from NSCLC group.CD8+T cells were stimulated with recombinant IL-9.Cellular proliferation and perforin/granzyme B level were investigated.Th9 cells and/or CD8+T cells were cocultured with primary NSCLC cells.The effect of IL-9 on cytolytic and noncytolytic activity of CD8+T cells was assessed.Student t test,paired t test,and Wilcoxon paired test were used for comparison.Results:Compared with control group,percentage of Th9 cells,IL-9 level,and PU.1 mRNA relative level in peripheral blood were lower in NSCLC group(all P<0.0001).Percentage of Th9 cells,IL-9 level,and PU.1 mRNA relative level in BALF isolated from tumor site were also lower than those of non-tumor site in NSCLC group(all P<0.0001).IL-9 stimulation promoted the proliferation and periforin/granzyme B secretion of CD8+T cells in NSCLC group.IL-9 stimulation also enhanced the cytolytic and noncytolytic activity of CD8+T cells in NSCLC group to primary NSCLC patients,which presented as increased target cell death and interferon-γ/tumor necrosis factor-α secretion.Th9 cells also increased the cytolytic and noncytolytic activity of CD8+T cells in NSCLC group,while anti-IL-9 neutralization antibody inhibited the regulatory function of Th9 cell to CD8+T cells.Conclusion:Th9 cells may enhance anti-tumor activity of CD8+T cells probably via IL-9 secretion in NSCLC patients.

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更新日期/Last Update: 2021-01-05