NK细胞联合PD-1单抗杀伤结直肠癌细胞的研究

doi:10.11904/j.issn.1002-3070.2023.02.007

实用肿瘤学杂志 ›› 2023, Vol. 37 ›› Issue (2): 130-136.doi: 10.11904/j.issn.1002-3070.2023.02.007

NK细胞联合PD-1单抗杀伤结直肠癌细胞的研究

王丙萍¹, 段金凯², 张双³, 高艳伟³, 任猛³, 陈良全³, 高维实³

1.内蒙古自治区人民医院肿瘤研究所(呼和浩特 010017);
2.内蒙古建筑职业技术学院公共课教学部;
3.内蒙古自治区人民医院腹部肿瘤外科

收稿日期:2022-07-06 修回日期:2023-03-07 发布日期:2023-05-30
通讯作者: 王丙萍,E-mail:wangbingping77@163.com
作者简介:王丙萍,女,(1985-),博士,助理研究员,从事肿瘤免疫治疗的研究。
基金资助:
内蒙古自治区科技计划项目(编号:2022YFSH0055);内蒙古自治区自然科学基金(编号:2021LHMS08060)

Research on NK cells combined with PD-1 monoclonal antibody to kill colorectal cancer cells

WANG Bingping¹, DUAN Jinkai², ZHANG Shuang³, GAO Yanwei³, REN Meng³, CHEN Liangquan³, GAO Weishi³

1. Cancer Institute,Inner Mongolia People′s Hospital,Hohhot 010017,China;
2. Department of Public Education,Inner Mongolia Technical College of Construction;
3. Department of Abdominal Oncology Surgery,Inner Mongolia People′s Hospital

Received:2022-07-06 Revised:2023-03-07 Published:2023-05-30

摘要/Abstract

摘要： 目的通过检测NK细胞及PD-1单抗+NK细胞杀伤五种结直肠癌细胞系的效率,鉴定NK细胞过继性回输治疗结直肠癌的可行性及探索新的治疗策略。方法通过体外诱导外周血单个核细胞的方法培养NK细胞,CCK-8法检测NK细胞及PD-1单抗+NK细胞杀伤五种结直肠癌细胞系LOVO、Caco-2、HT-29、HT-115和HRT-18的效率及效靶比,通过统计比较两种效应组对结直肠癌细胞系的杀伤效果。结果 NK细胞对五种靶细胞的杀伤效率差异显著(P＜0.01);NK细胞对同一种靶细胞的杀伤效率在不同效靶比时差异显著(P＜0.05);PD-1单抗与NK细胞联合应用对Caco-2(效靶比2∶1)、HT-29(效靶比5∶1和10∶1)以及HT-115(效靶比0.1∶1和0.5∶1)细胞系的杀伤效率与单独NK细胞相比差异显著(P＜0.05),其余各组间差异均无统计学意义(P＞0.05)。结论应用NK细胞过继回输治疗结直肠癌时,将效靶比控制在2∶1时可能是一个安全且治疗效果最好的比例;NK细胞对结直肠癌的杀伤效率与其分化程度无关;PD-1单抗可以联合NK细胞过继性回输治疗结直肠癌且有一定的治疗意义。

关键词: NK细胞, PD-1单抗, 结直肠癌, 效靶比, 联合治疗

Abstract: Objective The Objective of this study was to identify the feasibility of adoptive reinfusion in NK cells to treat colorectal cancer and to explore new therapeutic strategies by detecting the killing efficiency of NK cells and PD-1 monoclonal antibody(mAb)+ NK cells in five kinds of colorectal cancer cell lines. Methods NK cells were cultured by inducing peripheral blood mononuclear cells in vitro,and a CCK-8 assay was used to detect NK cells and PD-1 mAb + NK cells to kill the efficiency of five colorectal cancer LOVO,Caco-2,HT-29,HT-115 and HRT-18 cell lines,the ratio of effect-to-target,and compare the killing effects of the two effector groups on colorectal cancer cells through statistics. Results The killing efficiencies of NK cells against the five target cells were significantly different(P＜0.01).The killing efficiencies of NK cells against the same target cells were significantly different at different effect target ratios(P＜0.05).The killing efficiencies of PD-1 mAb combined with NK cells on Caco-2(effect-target-ratio 2∶1),HT-29(effect-target-ratio 5∶1 and 10∶1)and HT-115(effect-target-ratio 0.1∶1 and 0.5∶1)cells were significantly different from those of NK cells alone(P＜0.05),and there was no significant difference among other groups(P＞0.05). Conclusion When using NK cells adoptive transfusion to treat colorectal cancer,controlling the effect-target ratio at 2:1 may be a safe and effective ratio;Killing efficiency of NK cells on colorectal cancer has nothing to do with its degree of differentiation;PD-1 mAb can be combined with adoptive reinfusion of NK cells in the treatment of colorectal cancer and has certain therapeutic significance.

Key words: NK cells, PD-1 mAb, Colorectal cancer, Effect-target ratio, Combination therapy

中图分类号:

王丙萍, 段金凯, 张双, 高艳伟, 任猛, 陈良全, 高维实. NK细胞联合PD-1单抗杀伤结直肠癌细胞的研究[J]. 实用肿瘤学杂志, 2023, 37(2): 130-136.

WANG Bingping, DUAN Jinkai, ZHANG Shuang, GAO Yanwei, REN Meng, CHEN Liangquan, GAO Weishi. Research on NK cells combined with PD-1 monoclonal antibody to kill colorectal cancer cells[J]. Journal of Practical Oncology, 2023, 37(2): 130-136.

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http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2023/V37/I2/130

参考文献

1 Sung H,Ferlay J,Siegel RL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2021,71(3):209-249.
2 Mueller M,Schneider MA,Deplazes B,et al.Colorectal cancer of the young displays distinct features of aggressive tumor biology:a single-center cohort study[J].World J Gastrointest Surg,2021,13(2):164-175.
3 Shiravand Y,Khodadadi F,Kashani SMA,et al.Immune checkpoint inhibitors in cancer therapy[J].Curr Oncol,2022,29(5):3044-3060.
4 Doki Y,Ajani JA,Kato K,et al.Nivolumab combination therapy in advanced esophageal squamous-cell carcinoma[J].N Engl J Med,2022,386(5):449-462.
5 Xie W,Medeiros LJ,Li S,et al.PD-1/PD-L1 pathway and its blockade in patients with classic hodgkin lymphoma and non-hodgkin large-cell lymphomas[J].Curr Hematol Malig Rep,2020,15(4):372-381.
6 Kreidieh M,Mukherji D,Temraz S,et al.Expanding the scope of immunotherapy in colorectal cancer:current clinical approaches andfuture directions[J].Biomed Res Int,2020,2020:9037217.
7 ZHANG X,WU T,CAI X,et al.Neoadjuvant immunotherapy for MSI-H/dMMR locally advanced colorectal cancer:new strategies and unveiled opportunities[J].Front Immunol,2022,13:795972.
8 HU W,WANG G,HUANG D,et al.Cancer immunotherapy based on natural killer cells:current progress and new opportunities[J].FrontImmunol,2019,10:1205.
9 Tanaka J,Miller J S.Recent progress in and challenges in cellular therapy using NK cells for hematological malignancies[J].Blood Rev,2020,44:100678.
10 LIN M,LUO H,Liang S,et al.Pembrolizumab plus allogeneic NK cells in advanced non-small cell lung cancer patients[J].J Clin Invest,2020,130(5):2560-2569.
11 ZHANG X,YANG R,WU T,et al.Efficacy and safety of Neoadjuvant monoimmunotherapy with PD-1 inhibitor for dMMR/MSI-H locally advanced colorectal cancer:a single-center real-world study[J].Front Immunol,2022,13:913483.
12 Quirin H,Timo R,Chiara R.Natural killer cell specificity for viral infections[J].Nature Immunology,2018,19(8):800-808.
13 Sivori S,Pende D,Quatrini L,et al.NK cells and ILCs in tumor immunotherapy[J].Mol Aspects Med,2020,80:100870.
14 YE L,ZHANG F,LI H,et al.Circulating tumor cells were associated with the number of T lymphocyte subsets and NK cells in peripheral blood in advanced non-small-cell lung cancer[J].Dis Markers,2017:5727815.
15 牟冠男,马强.NK细胞极化在子宫内膜癌中的作用[J].实用肿瘤学杂志,2021,35(6):534-537.

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NK细胞联合PD-1单抗杀伤结直肠癌细胞的研究

Research on NK cells combined with PD-1 monoclonal antibody to kill colorectal cancer cells

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