扩增的NK细胞对胃癌细胞的杀伤作用及其机制

doi:10.13481/j.1671-587x.20200317

Abstract

Abstract: Objective: To investigate the killing effect of amplified natural killer (NK) cells on the gastric cancer cells,and to elucidate its mechanism. Methods: The peripheral blood mononuclear cells (PBMCs) from 15 patients with gastric cancer were extracted and isolated. The morphology of NK cells before and after amplification was observed, the percentages of NK cells before and after amplification were detected, and the amplification time of NK cells after amplification was calculated.The killing effects of NK cells on the gastric cancer cells before and after amplification were detected. The percentages of expressions of killing activating receptors NKG2D and DNAM-1 and killing inhibitory receptors KIR2DL1 and KIR3DL1 were detected by flow cytometry. Results: Before amplification, the NK cells were round, small in size and scattered in distribution. After amplification, the NK cells were increased in size and irregular in shape. The percentage of NK cells after amplification was significantly higher than that before amplification (P<0.01), and the number of the NK cells after amplification was (596±152) times of before amplification. When the effective target ratio was 5:1, the killing activity of NK cells on the gastric cancer cells after amplification was significantly higher than that before amplification (P<0.01).After amplification, the percentages of expressions of killing activating receptors NKG2D and DNAM-1 were significantly higher than those before amplification (P<0.01).After amplification, the percentages of expressions of killing inhibitory receptors KIR2DL1 and KIR3DL1 were significantly lower than those before amplification (P<0.05). Conclusion: The killing effect of NK cells on the gastric cancer cells after amplification is stronger than before amplification. The mechanism may be related to increasing the expressions of activated receptors and decreasing the expressions of inhibitory receptors on the surface of NK cells after amplification.

Key words: natural killer cells, stomach neoplasms, killing effect, killing activating receptor, killing inhibitory receptor

CLC Number:

R730.51

SHI Guanghuan, ZHOU Shiping, XU Dongsheng, WANG Xiu. Killing effect of amplified NK cells on gastric cancer cells and its mechanism[J].Journal of Jilin University(Medicine Edition), 2020, 46(03): 530-535.

References

[1] FANG F, XIAO WH, TIAN Z G. NK cell-based immunotherapy for cancer[J]. Semin Immunol, 2017, 31:37-54.
[2] FEHNIGER T A, COOPER M A. Harnessing NK cell memory for cancer immunotherapy[J]. Trends Immunol, 2016, 37(12):877-888.
[3] BASSANI B, BACI D, GALLAZZI M, et al. Natural killer cells as key players of tumor progression and angiogenesis:old and novel tools to divert their pro-tumor activities into potent anti-tumor effects[J]. Cancers (Basel), 2019, 11(4):E461.
[4] XIE S L, WU Z Y, NIU L Z, et al. Preparation of highly activated natural killer cells for advanced lung cancer therapy[J]. Oncol Targets Ther, 2019, 12:5077-5086.
[5] JUENGPANICH S, SHI L, IRANMANESH Y, et al. The role of natural killer cells in hepatocellular carcinoma development and treatment:A narrative review[J]. Transl Oncol, 2019, 12(8):1092-1107.
[6] 雷子颖, 王俞, 罗嘉莉, 等. 胃癌患者外周血T淋巴细胞亚群和NK细胞分析[J]. 消化肿瘤杂志(电子版), 2018, 10(4):196-199.
[7] HAN B, MAO F Y, ZHAO Y L, et al. Altered NKp30, NKp46, NKG2D, and DNAM-1 expression on circulating NK cells is associated with tumor progression in human gastric cancer[J]. J Immunol Res, 2018, 2018:6248590.
[8] DU Y, WEI Y. Therapeutic potential of natural killer cells in gastric cancer[J]. Front Immunol, 2018, 9:3095.
[9] REZVANI K, ROUCE R, LIU E L, et al. Engineering natural killer cells for cancer immunotherapy[J]. Mol Ther, 2017, 25(8):1769-1781.
[10] MARTIN-ANTONIO B, SUNE G, PEREZ-AMILL L, et al. Natural killer cells:angels and devils for immunotherapy[J]. Int J Mol Sci, 2017, 18(9):E1868.
[11] LI X M, HE C H, LIU C Z, et al. Expansion of NK cells from PBMCs using immobilized 4-1BBL and interleukin-21[J]. Int J Oncol, 2015, 47(1):335-342.
[12] MUNTASELL A, OCHOA M C, CORDEIRO L, et al. Targeting NK-cell checkpoints for cancer immunotherapy[J]. Curr Opin Immunol, 2017, 45:73-81.
[13] PHAN M T, LEE S H, KIM S K, et al. Expansion of NK cells using genetically engineered k562 feeder cells[J]. Methods Mol Biol, 2016, 1441:167-174.
[14] CHENG H Y, YE X, MA R Q, et al. Experiment research of natural killer cells amplification in vitro and the killing effect on ovarian cancer cells[J]. Zhonghua Fu Chan Ke Za Zhi, 2017, 52(8):545-550.
[15] LAPTEVA N, DURETT A G, SUN J L, et al. Large-scale ex vivo expansion and characterization of natural killer cells for clinical applications[J]. Cytotherapy, 2012, 14(9):1131-1143.
[16] LUHM J, BRAND J M, KORITKE P, et al. Large-scale generation of natural killer lymphocytes for clinical application[J]. J Hematother Stem Cell Res, 2002, 11(4):651-657.
[17] CHILDS R W, BERG M. Bringing natural killer cells to the clinic:ex vivo manipulation[J]. Hematol Am Soc Hematol Edu Program, 2013, 2013:234-246.
[18] GRANZIN M, WAGNER J, KOHL U, et al. Shaping of natural killer cell antitumor activity by ex vivo cultivation[J]. Front Immunol, 2017, 8:458.
[19] WAGNER J, PFANNENSTIEL V, WALDMANN A, et al. A two-phase expansion protocol combining interleukin (IL)-15 and IL-21 improves natural killer cell proliferation and cytotoxicity against rhabdomyosarcoma[J]. Front Immunol, 2017, 8:676.
[20] VIVIER E, TOMASELLO E, BARATIN M, et al. Functions of natural killer cells[J]. Nat Immunol, 2008, 9(5):503-510.
[21] KRASNOVA Y, PUTZ E M, SMYTH M J, et al. Bench to bedside:NK cells and control of metastasis[J]. Clin Immunol, 2017, 177:50-59.
[22] CAROTTA S. Targeting NK cells for anticancer immunotherapy:clinical and preclinical approaches[J]. Front Immunol, 2016, 7:152.
[23] OCHOA M C, MINUTE L, RODRIGUEZ I, et al. Antibody-dependent cell cytotoxicity:immunotherapy strategies enhancing effector NK cells[J]. Immunol Cell Biol, 2017, 95(4):347-355.
[24] HILTON H G, PARHAM P. Missing or altered self:human NK cell receptors that recognize HLA-C[J]. Immunogenetics, 2017, 69(8/9):567-579.
[25] TU M M, MAHMOUD A B, MAKRIGIANNIS A P. Licensed and unlicensed NK cells:differential roles in cancer and viral control[J]. Front Immunol, 2016, 7:166.
[26] 贺丽娜,胡杨志,周轩,等.沉默PROX1表达对胃癌AGS细胞增殖和侵袭能力的影响[J].郑州大学学报(医学版),2019,54(4):559-563.

Killing effect of amplified NK cells on gastric cancer cells and its mechanism

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Metrics

Comments

Recommended 0

[1]	XU Jianguo, CAO Hongtao, ZHANG Zilong, JI Baoyan, WANG Chunqiu, LI Shengdong, LIU Guoqing. Effects of LincRNA-p21 knockdown on growth and metastasis of gastric cancer cells and their mechanisms [J]. Journal of Jilin University(Medicine Edition), 2020, 46(02): 266-273.
[2]	YUAN Huqin, LI Qiang. Effects of oxaliplatin combined with capecitabine on expressions oftumor-related factors in gastric cancer tissue of rats with experimental gastric cancer and their synergistic anti-tumor effects [J]. Journal of Jilin University(Medicine Edition), 2019, 45(04): 784-789.
[3]	GAO Fang, MA Licong, DONG Wenjie, TIAN Xuyang, DANG Tong, JIA Yanbin. Analysis on association between single nucleotide polymorphisms of ITGA1 gene and risk of non-cardia gastric cancer [J]. Journal of Jilin University(Medicine Edition), 2019, 45(03): 577-581.
[4]	ZHANG Haolong, YU Zhentao, GAO Zihan, WU Yuanyu, FANG Xuedong. Related risk factors and clinical treatment of patients with PGS after gastric cancer operation [J]. Journal of Jilin University(Medicine Edition), 2019, 45(03): 673-677.
[5]	ZHU Guangwei, HUANG Jinsheng, HUANG Yongjian, ZHENG Wei, YANG Shugang, LIN Chunlin, CHEN Hengkai, YE Jianxin. Construction of lentiviral vector with overexpression of ERp29 and its effect on biological behavior of gastric cancer cells [J]. Journal of Jilin University(Medicine Edition), 2019, 45(02): 244-250.
[6]	WANG Xinmeng, LI Qiyang, LIU Chao, XIAO Jianying. Effects of microspherule protein 1 on invasion and migration of gastric cancer cells and their mechanisms [J]. Journal of Jilin University(Medicine Edition), 2019, 45(02): 251-257.
[7]	LU Mingyue, LI Jing. Relationships between expression of IGF-1 in cancer tissue of gastric cancer patients and clinicopathological parameters in China: A Meta-analysis [J]. Journal of Jilin University(Medicine Edition), 2019, 45(01): 137-142.
[8]	MU Tianchi, LIU Chao, FU Shuai, LI Qiyang, WANG Xinmeng, XIAO Jianying. Expression of activator of basal transcription 1 in gastric cancer tissue and its clinical significance [J]. Journal of Jilin University(Medicine Edition), 2019, 45(01): 94-99.
[9]	ZHAO Dan, CAO Donghui, JIN Meishan, WU Menghui, WANG Yueqi, YANG Na, ZHOU Tianyu, ZHANG Houjun, JIANG Jing, CAO Xueyuan. Inhibitory effect of 18β-glycyrrhetinic acid on inflammation-related gastric cancer and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2018, 44(06): 1150-1155.
[10]	YANG Dongye, JIAO Yang, TAN Bibo, DU Zhijian, HU Xiaojie, LIU Fei. Expression of Gli1 in gastric carcinoma tissue and its effect on biological characteristics of gastric carcinoma cells [J]. Journal of Jilin University Medicine Edition, 2018, 44(01): 63-67.
[11]	LIU Gang, ZHAO Minxue, WANG Desheng. Application of detection of serum pepsinogen, gastrin-17 and Helicobacter pylori antibody in gastric cancer screening [J]. Journal of Jilin University Medicine Edition, 2017, 43(06): 1182-1185.
[12]	KONG Guimei, WANG Jijun, TAO Wenhua, BU Ping, QIAN Feng. Expression of PRMT5 in human gastric cancer tissue and its significance [J]. Journal of Jilin University Medicine Edition, 2016, 42(04): 753-756.
[13]	YOU Lili, CAO Donghui, JIANG Jing, LIU Ruming, MA Lin, WANG Shidong, SUO Yueer, HOU Zhen, CAO Xueyuan. Inhibitory effect of 18β-glycyrrhetinic acid on gastric tumor in K19-C2mE transgenic mice and its mechanisms [J]. Journal of Jilin University Medicine Edition, 2016, 42(02): 221-225.
[14]	JI Guofeng, TAO Youmao, LI Zhuo, MA Chong, XIAO Ling. Analysis on risk factors of infections in patients with gastric cancerafter laparoscope-assisted distal gastrectomy [J]. Journal of Jilin University Medicine Edition, 2015, 41(05): 1076-1079.
[15]	ZHANG Huijian, DANG Qiang, YIN Haixia, PENG Peidan, LIU Chengshan, HUANG Yuxian. Synergistic effect of sunitinib combined with NK cells on renal clear cell carcinoma cell lines and its mechanism [J]. Journal of Jilin University Medicine Edition, 2015, 41(04): 742-746.