基于NK细胞的免疫治疗在肝癌中的研究进展

程世纪; 匡天瑞; 董可帅; 余佳

doi:10.3969/j.issn.1001-5256.2023.06.034

基于NK细胞的免疫治疗在肝癌中的研究进展

DOI: 10.3969/j.issn.1001-5256.2023.06.034

武汉大学人民医院肝胆外科，武汉 430060

基金项目:

国家自然科学基金 (82003063);

武汉大学学位与研究生教育改革研究项目 (1605-413200097)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：程世纪负责查找文献，撰写文章；匡天瑞、董可帅负责修改文章; 余佳负责指导撰写文章并最后定稿。

详细信息

通信作者:
余佳，hbpennhmp116@163.com (ORCID：0000-0002-2503-0025)

计量
- 文章访问数: 613
- HTML全文浏览量: 139
- PDF下载量: 66
- 被引次数: 0
出版历程
- 收稿日期: 2022-09-18
- 录用日期: 2022-11-10
- 出版日期: 2023-06-20

Research advances in natural killer cell-based immunotherapy in liver cancer

Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China

Research funding:

National Natural Science Foundation of China (82003063);

Research Project of Degree and Postgraduate Education Reform of Wuhan University (1605-413200097)

More Information

Corresponding author: YU Jia, hbpennhmp116@163.com (ORCID: 0000-0002-2503-0025)

摘要

摘要: 自然杀伤细胞(NK细胞)是人体重要的免疫细胞，也是肝内主要的淋巴细胞，被认为是抵御肿瘤的第一道防线，对肝癌发生发展有重大影响。NK细胞所具有的特性，使其成为免疫治疗的新选择，基于NK细胞的免疫疗法或将在肝癌治疗中取得成功。本文就NK细胞的生物学特征、其在肝癌发生发展中的作用及相关治疗中的研究进展进行综述。
- 肝肿瘤 /
- 杀伤细胞 /
- 天然 /
- 免疫疗法
Abstract: Natural killer (NK) cells are important immune cells in the human body and are also the main lymphocytes in the liver. They are considered the first defense mechanism against tumor and have a significant impact on the development and progression of liver cancer. The characteristics of NK cells help them become a new choice for immunotherapy, and NK cell-based immunotherapy may succeed in the treatment of liver cancer. This article reviews the biological characteristics of NK cells, their role in the development and progression of liver cancer, and the research advances in related treatment.
- Liver Neoplasms /
- Killer Cells /
- Natural /
- Immunotherapy

HTML全文

参考文献(44)

[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. DOI: 10.3322/caac.21660.
[2]	SAJID M, LIU L, SUN C. The dynamic role of NK cells in liver cancers: role in HCC and HBV associated HCC and its therapeutic implications[J]. Front Immunol, 2022, 13: 887186. DOI: 10.3389/fimmu.2022.887186.
[3]	LI J, TAO L, WANG X. Cytotoxic immune cell-based immunotherapy for hepatocellular carcinoma[J]. Hepatoma Research, 2020, 6: 15. DOI: 10.20517/2394-5079.2019.34.
[4]	MARQUARDT N, BÉZIAT V, NYSTRÖM S, et al. Cutting edge: identification and characterization of human intrahepatic CD49a⁺ NK cells[J]. J Immunol, 2015, 194(6): 2467-2471. DOI: 10.4049/jimmunol.1402756.
[5]	MICHEL T, OLLERT M, ZIMMER J. A hot topic: Cancer immunotherapy and natural killer cells[J]. Int J Mol Sci, 2022, 23(2): 797. DOI: 10.3390/ijms23020797.
[6]	KALATHIL SG, THANAVALA Y. Natural killer cells and T cells in hepatocellular carcinoma and viral hepatitis: Current status and perspectives for future immunotherapeutic approaches[J]. Cells, 2021, 10(6). DOI: 10.3390/cells10061332.
[7]	LIU P, CHEN L, ZHANG H. Natural killer cells in liver disease and hepatocellular carcinoma and the NK cell-based immunotherapy[J]. J Immunol Res, 2018, 2018: 1206737. DOI: 10.1155/2018/1206737.
[8]	POZNANSKI SM, SINGH K, RITCHIE TM, et al. Metabolic flexibility determines human NK cell functional fate in the tumor microenvironment[J]. Cell Metab, 2021, 33(6): 1205-1220. e5. DOI: 10.1016/j.cmet.2021.03.023.
[9]	OURA K, MORISHITA A, TANI J, et al. Tumor immune microenvironment and immunosuppressive therapy in hepatocellular carcinoma: a review[J]. Int J Mol Sci, 2021, 22(11): 5801. DOI: 10.3390/ijms22115801.
[10]	MIKULAK J, BRUNI E, ORIOLO F, et al. Hepatic natural killer cells: Organ-specific sentinels of liver immune homeostasis and physiopathology[J]. Front Immunol, 2019, 10: 946. DOI: 10.3389/fimmu.2019.00946.
[11]	PESCE S, GREPPI M, TABELLINI G, et al. Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization[J]. J Allergy Clin Immunol, 2017, 139(1): 335-346. e3. DOI: 10.1016/j.jaci.2016.04.025.
[12]	WONG J, KWOK G, TANG V, et al. Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors[J]. J Immunother Cancer, 2021, 9(2): e001945. DOI: 10.1136/jitc-2020-001945.
[13]	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. DOI: 10.1172/JCI132712.
[14]	BARRUETO L, CAMINERO F, CASH L, et al. Resistance to checkpoint inhibition in cancer immunotherapy[J]. Transl Oncol, 2020, 13(3): 100738. DOI: 10.1016/j.tranon.2019.12.010.
[15]	TAN S, XU Y, WANG Z, et al. Tim-3 hampers tumor surveillance of liver-resident and conventional NK cells by disrupting PI3K signaling[J]. Cancer Res, 2020, 80(5): 1130-1142. DOI: 10.1158/0008-5472.CAN-19-2332.
[16]	DEUSS FA, WATSON GM, FU Z, et al. Structural basis for CD96 immune receptor recognition of nectin-like protein-5, CD155[J]. Structure, 2019, 27(2): 219-228. e3. DOI: 10.1016/j.str.2018.10.023.
[17]	STAMM H, OLIVEIRA-FERRER L, GROSSJOHANN EM, et al. Targeting the TIGIT-PVR immune checkpoint axis as novel therapeutic option in breast cancer[J]. Oncoimmunology, 2019, 8(12): e1674605. DOI: 10.1080/2162402X.2019.1674605.
[18]	SUN H, HUANG Q, HUANG M, et al. Human CD96 correlates to natural killer cell exhaustion and predicts the prognosis of human hepatocellular carcinoma[J]. Hepatology, 2019, 70(1): 168-183. DOI: 10.1002/hep.30347.
[19]	AHN M, NIU J, KIM D, et al. Vibostolimab, an anti-TIGIT antibody, as monotherapy and in combination with pembrolizumab in anti-PD-1/PD-L1-refractory NSCLC[J]. Ann Oncol, 2020, 31: S887. DOI: 10.1016/j.annonc.2020.08.1714.
[20]	BLAKE SJ, DOUGALL WC, MILES JJ, et al. Molecular pathways: Targeting CD96 and TIGIT for cancer immunotherapy[J]. Clin Cancer Res, 2016, 22(21): 5183-5188. DOI: 10.1158/1078-0432.CCR-16-0933.
[21]	BUCKLE I, GUILLEREY C. Inhibitory receptors and immune checkpoints regulating natural killer cell responses to cancer[J]. Cancers (Basel), 2021, 13(17): 4263. DOI: 10.3390/cancers13174263.
[22]	KOHRT HE, THIELENS A, MARABELLE A, et al. Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies[J]. Blood, 2014, 123(5): 678-686. DOI: 10.1182/blood-2013-08-519199.
[23]	ZHANG J, BASHER F, WU JD. NKG2D ligands in tumor immunity: two sides of a coin[J]. Front Immunol, 2015, 6: 97. DOI: 10.3389/fimmu.2015.00097.
[24]	OLIVIERO B, VARCHETTA S, MELE D, et al. MICA/B-targeted antibody promotes NK cell-driven tumor immunity in patients with intrahepatic cholangiocarcinoma[J]. Oncoimmunology, 2022, 11(1): 2035919. DOI: 10.1080/2162402X.2022.2035919.
[25]	FERRARI DE ANDRADE L, TAY RE, PAN D, et al. Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity[J]. Science, 2018, 359(6383): 1537-1542. DOI: 10.1126/science.aao0505.
[26]	FELICES M, LENVIK TR, DAVIS ZB, et al. Generation of biKEs and triKEs to improve NK cell-Mediated targeting of tumor cells[J]. Methods Mol Biol, 2016, 1441: 333-346. DOI: 10.1007/978-1-4939-3684-7_28.
[27]	van FAASSEN H, JO D, RYAN S, et al. Incorporation of a novel CD16-specific single-domain antibody into multispecific natural killer cell engagers with potent ADCC[J]. Mol Pharmaceut, 2021, 18(6): 2375-2384. DOI: 10.1021/acs.molpharmaceut.1c00208.
[28]	ABEL AM, YANG C, THAKAR MS, et al. Natural killer cells: development, maturation, and clinical utilization[J]. Front Immunol, 2018, 9: 1869. DOI: 10.3389/fimmu.2018.01869.
[29]	MADDINENI S, SILBERSTEIN JL, SUNWOO JB. Emerging NK cell therapies for cancer and the promise of next generation engineering of iPSC-derived NK cells[J]. J Immunother Cancer, 2022, 10(9): e004693. DOI: 10.1136/jitc-2022-004693.
[30]	KLINGEMANN H, BOISSEL L, TONEGUZZO F. Natural killer cells for immunotherapy-advantages of the NK-92 cell line over blood NK cells[J]. Front Immunol, 2016, 7: 91. DOI: 10.3389/fimmu.2016.00091.
[31]	BERGMAN H, LINDQVIST C. Human IL-15 inhibits NK cells specific for human NK-92 cells[J]. Anticancer Res, 2021, 41(7): 3281-3285. DOI: 10.21873/anticanres.15114.
[32]	DAI K, WU Y, SHE S, et al. Advancement of chimeric antigen receptor-natural killer cells targeting hepatocellular carcinoma[J]. World J Gastrointest Oncol, 2021, 13(12): 2029-2037. DOI: 10.4251/wjgo.v13.i12.2029.
[33]	DAHER M, MELO GARCIA L, LI Y, et al. CAR-NK cells: the next wave of cellular therapy for cancer[J]. Clin Transl Immunology, 2021, 10(4): e1274. DOI: 10.1002/cti2.1274.
[34]	YU M, LUO H, FAN M, et al. Development of GPC3-specific chimeric antigen receptor-engineered natural killer cells for the treatment of hepatocellular carcinoma[J]. Mol Ther, 2018, 26(2): 366-378. DOI: 10.1016/j.ymthe.2017.12.012.
[35]	ZHAO J, LIN L, LUO Y, et al. Optimization of GPC3-specific chimeric antigen receptor structure and its effect on killing hepatocellular carcinoma cells[J]. Bioengineered, 2021, 12(1): 3674-3683. DOI: 10.1080/21655979.2021.1950261.
[36]	TSENG HC, XIONG W, BADETI S, et al. Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma[J]. Nat Commun, 2020, 11(1): 4810. DOI: 10.1038/s41467-020-18444-2.
[37]	ZHU H, BLUM RH, BERNAREGGI D, et al. Metabolic reprograming via deletion of CISH in Human iPSC-Derived NK cells promotes in vivo persistence and enhances anti-tumor activity[J]. Cell Stem Cell, 2020, 27(2): 224-237. e6. DOI: 10.1016/j.stem.2020.05.008.
[38]	NAEIMI KARAROUDI M, NAGAI Y, ELMAS E, et al. CD38 deletion of human primary NK cells eliminates daratumumab-induced fratricide and boosts their effector activity[J]. Blood, 2020, 136(21): 2416-2427. DOI: 10.1182/blood.2020006200.
[39]	ALLAN D, CHAKRABORTY M, WALLER GC, et al. Systematic improvements in lentiviral transduction of primary human natural killer cells undergoing ex vivo expansion[J]. Mol Ther Methods Clin Dev, 2021, 20: 559-571. DOI: 10.1016/j.omtm.2021.01.008.
[40]	FERNANDEZ JP, LUDDY KA, HARMON C, et al. Hepatic tumor microenvironments and effects on NK cell phenotype and function[J]. Int J Mol Sci, 2019, 20(17): 4131. DOI: 10.3390/ijms20174131.
[41]	ZHUANG L, FULTON RJ, RETTMAN P, et al. Activity of IL-12/15/18 primed natural killer cells against hepatocellular carcinoma[J]. Hepatol Int, 2019, 13(1): 75-83. DOI: 10.1007/s12072-018-9909-3.
[42]	ZHENG X, QIAN Y, FU B, et al. Mitochondrial fragmentation limits NK cell-based tumor immunosurveillance[J]. Nat Immunol, 2019, 20(12): 1656-1667. DOI: 10.1038/s41590-019-0511-1.
[43]	YANG Y, LUNDQVIST A. Immunomodulatory effects of IL-2 and IL-15; Implications for cancer immunotherapy[J]. Cancers (Basel), 2020, 12(12): 3586. DOI: 10.3390/cancers12123586.
[44]	MASKALENKO NA, ZHIGAREV D, CAMPBELL KS. Harnessing natural killer cells for cancer immunotherapy: dispatching the first responders[J]. Nat Rev Drug Discov, 2022, 21(8): 559-577. DOI: 10.1038/s41573-022-00413-7.