肺癌模型小鼠肿瘤和主要免疫器官组织中调节性T细胞和NK细胞的数量变化及其意义

doi:10.13481/j.1671-587x.20160405

Abstract

Abstract:

Objective: To explore the changes of number of CD4⁺CD25⁺foxp3⁺ regulatory T cells (Treg) and natural killer cells (NK) inthe peripheral immune organs and tumor tissue of the murine models of lung cancer,and to clarify their effects on the development of lung cancer. Methods: The C57BL/6 mice were divided into Lewis lung carcinoma cells (LLC) injection group and normal control group. The mice in LLC injection group were injected with LLC subcutaneously in the armpit to establish the tumor models,while the mice in normal control group were injected with the same amount of saline. The number of CD4⁺CD25⁺T cells,CD4⁺CD25⁺ foxp3⁺Tregs in the spleen,lymph nodes and lung cancer tissues,and the number of NK cells in the spleen tissue were labeled by cell surface or intracellular antibody staining,and detected by flow cytometry. Results: The ratios of CD4⁺CD25⁺T cells to CD4⁺T cells,foxp3⁺ cells to CD4⁺CD25⁺ T cells,and the number of CD4⁺CD25⁺foxp3⁺ Treg in the spleen and lymph nodes of the mice in LLC injection group were increased significantly compared with normal control group(P<0.05 or P<0.01). Moreover,the ratios of CD4⁺CD25⁺ T cells to CD4⁺ T cells and foxp3⁺ cells to CD4⁺CD25⁺T cells in the tumor tissue were significantly higher than those in the spleen and lymph nodes of the mice in LLC injection group. However,the ratio of NK cells in the spleen tissue of the mice in lung cancer group was significantly decreased compared with normal control group(P<0.05). Conclusion: The increase of ratio and the number of Treg cells and the decrease of ratio of NK cells in the main immune organs of lung cancer mice may promote the development of tumor and inhibit the immune response to cancer cells in vivo.

Key words: lung neoplasms, regulatory T cells, nature killer cells

CLC Number:

R392.11

ZHENG Quanhui, WANG Na, SONG Tianjiao, CAO Qianwen, TIAN Yu, HAO Xiaohui, ZHANG Aihong. Changes of number of regulatory T cells and NK cells in tumor tissue and main immune organs of murine models of lung cancer and their significances[J].Journal of Jilin University Medicine Edition, 2016, 42(04): 659-664.

References

[1] Campbell DJ,Koch MA. Phenotypic and functional specialization of FOXP3⁺regulatory T cells[J].Nat Rev Immunol,2011,11(2):119-130.

[2] Cheng M,Chen Y,Xiao W,et al. NK cell-based immunotherapy for malignant diseases[J]. Cell Mol Immunol,2013,10(3):230-252.

[3] 郑全辉,刘英文,张雪梅. 肺癌小鼠MDSC和T细胞变化[J].中国免疫学杂志,2015,31(5):595-599.

[4] Patel S,Vetale S,Teli P,et al.IL-10 production in non-small cell lung carcinoma patients is regulated by ERK,P38 and COX-2[J]. J Cell Mol Med,2012,16(3):531-544.

[5] Shi W,Li X,Cha Z,et al.Dysregulation of circulating follicular helper T cells in nonsmall cell lung cancer[J]. DNA Cell Biol,2014,33(6):355-360.

[6] Reppert S,Boross I,Koslowski M,et al.A role for T-bet-mediated tumour immune surveillance in anti-IL-17A treatment of lung cancer[J].Nat Commun,2011,2:600.

[7] Duan MC,Han W,Jin PW,et al. Disturbed Th17/Treg balance in patients with non-small cell lung cancer[J]. Inflammation,2015,38(6):2156-2165.

[8] 邹静,刘斌,陈雪华,等.肺癌患者外周血T淋巴细胞亚群变化特点及其临床意义[J].中国免疫学杂志,2010,26(11):1016-1020.

[9] 张瑞萍,徐冰心,王社论,等. 晚期非小细胞肺癌调节性T细胞与预后的关系[J]. 现代肿瘤医学, 2013,21(3):521-524.

[10] 赵霞,韩福才,苏文,等. 晚期肺癌患者外周血Treg细胞与NK细胞及其活化受体检测临床意义的探讨[J].中华肿瘤防治杂志,2011,18(13):1009-1012.

[11] 侯玉森,苏文,王艳峰,等.肺癌患者调节性T细胞与NK细胞活化受体NKG2D的相关性及其临床意义[J]. 肿瘤研究与临床,2012,24(9):597-599.

[12] Zhang Q,Furukawa K,Chen HH,et al. Metastatic potential of mouse Lewis lung cancer cells is regulated via ganglioside GM1 by modulating the matrix metalloprotease-9 localization in lipid rafts[J]. J Biol Chem,2006,281(26):18145-18155.

[13] Wang P,An F,Zhuang X,et al. Chronopharmacology and mechanism of antitumor effect of erlotinib in Lewis tumor-bearing mice[J].PLoS One,2014,9(7):e101720.

[14] Lindau D,Gielen P, Kroesen M,et al. The immunosuppressive tumour network:myeloid-derived suppressor cells,regulatory T cells and natural killer T cells[J].Immunology,2013,138(2):105-115.

[15] Hall BM,Verma ND,Tran GT,et al. Distinct regulatory CD4⁺T cell subsets;differences between naïve and antigen specific T regulatory cells[J]. Curr Opin Immunol,2011,23(5):641-647.

[16] Wieland E,Shipkova M. Lymphocyte surface molecules as immune activation biomarkers[J].Clin Biochem,2016,49(4/5):347-354.

[17] Feng LL,Wang X. Targeting foxp3⁺ regulatory T cells-related immunosuppression for cancer immunotherapy[J].Chin Med J (Engl),2010,123(22):3334-3342.

[18] Makkouk A,Weiner GJ. Cancer immunotherapy and breaking immune tolerance:new approaches to an old challenge[J]. Cancer Res,2015,75(1):5-10.

Changes of number of regulatory T cells and NK cells in tumor tissue and main immune organs of murine models of lung cancer and their significances

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Metrics

Comments

Recommended 0

[1]	WANG Dan, LI Yifei, LI Chun, DONG Zhiheng, DONG Ying, GAI Xiaodong. Relationships between expressions of B7-H1 and B7-H4 and Foxp3⁺ regulated T-cell infiltration in colorectal cancer tissue [J]. Journal of Jilin University Medicine Edition, 2018, 44(03): 543-547.
[2]	LIU Xiangliang, JI Wei, LI Li, ZHAO Yinghua, JIA Lin, WANG Zhiqiang, CHEN Xiao, LI Wei. Lung adenocarcinoma treated by Erlotinib HCL Tablets and chemotherapy combined with bevacizumab after drug resistance:A case report and literature review [J]. Journal of Jilin University Medicine Edition, 2017, 43(05): 1019-1024.
[3]	XIAO Yan, WANG Huan, WANG Shumin, GAO Ying. Lung cancer complicated with syndrome of inappropriate secretion of antidiuretic hormone:A report of 2 cases and literature review [J]. Journal of Jilin University Medicine Edition, 2017, 43(03): 643-645.
[4]	LI Xingxing, TAN Jingjin, JIANG Shan, WAHG Ke. Role of let-7 and HMGA2 in occurrence and development of lung cancer: Meta-analysis [J]. Journal of Jilin University Medicine Edition, 2016, 42(06): 1116-1125.
[5]	ZAO Hang, WANG XU, LI WEI. Influence of single nucleotide polymorphisms of CDA in prognosis of advanced non-small cell lung cancer patients treated with gemcitabine [J]. Journal of Jilin University Medicine Edition, 2016, 42(02): 316-320.
[6]	CHENG Xin, MA Yanru, LIU Yimin, DANG Yonghong, XING Haiqun, HU Nan. Application of ¹⁸FDG PET/CT in diagnosis of ectopic ACTH syndrome induced by lung cancer [J]. Journal of Jilin University Medicine Edition, 2015, 41(06): 1275-1278.
[7]	LI Shimeng, PAN Baoxiang, LI Tong, XIE Feng, WANG Hai. Correlation between expression of programmed cell death-ligand 1 protein and prognosis of lung cancer:A Meta-analysis [J]. Journal of Jilin University Medicine Edition, 2015, 41(05): 969-973.
[8]	WANG Peng, ZHOU Jieping, ZHAN Bihong, QIAN Liting, WU Aidong, FU Jie. Comparison of dose distribution between 5F-IMRT,VMAT, and Gyro-knife radiotherapy plans for small lung masses [J]. Journal of Jilin University Medicine Edition, 2015, 41(05): 1044-1049.
[9]	GONG Ping, LI Yun, LUO Rui, LI Hong, TAN Yupin, LONG Yi. Effect of intradermal inactivated Bacillus Calmette-Guérin vaccine on number of CD4⁺CD25⁺Treg cells and expression of CTLA-4 mRNA in asthmatic rats [J]. Journal of Jilin University Medicine Edition, 2015, 41(03): 517-521.
[10]	MA Jianmei, CHEN Cheng, LI Xueping. Effects of PEDF on proliferation,invasion and apoptosis of lung squamous cell carcinoma SK-MES-1 cells [J]. Journal of Jilin University Medicine Edition, 2015, 41(01): 6-9.
[11]	LIN Fengwu, CHENG Kunpeng, ZHANG Qiang, MA Wenduan, HAN Yangdong, QI Liangchen, MA Le, WANG Yang, ZHANG Chao. VATS right upper lobectomy and bronchoplasty:1 case report with literature review [J]. Journal of Jilin University Medicine Edition, 2015, 41(01): 169-171.
[12]	LIN Xing-yu,YANG Zhi-guang,ZHANG Peng,SHAO Guo-guang. Comparison of curative effects of lobectomy between C-VATS  and thoracotomy in aged patients with lung cancer  [J]. Journal of Jilin University Medicine Edition, 2014, 40(06): 1275-1279.
[13]	LIN Xue-jun,YAN Kang-kang,ZHAO Long-yu,BAO Hong-hong,LI Shuang,LIU Xiao-dong,LIU Xin. Meta-analysis on association between smoking and p53 gene mutation in patients with lung cancer  [J]. Journal of Jilin University Medicine Edition, 2014, 40(05): 1046-1050.
[14]	CHENG Yuan,ZHEN Yong-zhan,HAO Xiao-fang,WU Peng-yu,XIONG Ya-nan,LIU Zhi-yong,CUI He-qin. Inhibitory effect of miR-205 　targeted YES1 on proliferation of A549 cells [J]. Journal of Jilin University Medicine Edition, 2014, 40(03): 493-498.
[15]	CAO He，LI Wei，QIAN Lei，WANG Xue-mei，CUI Jiu-wei. Inhibitory effect of COPS3 gene interferred by RNA on proliferation of lung cancer A549 cells and its mechanism [J]. Journal of Jilin University Medicine Edition, 2014, 40(02): 238-242.