|本期目录/Table of Contents|

[1]蒋伟,李涛综述,季国忠审校.原发性肝癌免疫治疗的研究进展[J].医学研究与战创伤救治(原医学研究生学报),2019,21(6):625-630.[doi:10.3969/j.issn.1672-271X.2019.06.016]
　JIANG Wei,LI Tao reviewing,JI Guo-zhong checking.The research progress of immunotherapy in hepatocellular carcinoma[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2019,21(6):625-630.[doi:10.3969/j.issn.1672-271X.2019.06.016]
点击复制

原发性肝癌免疫治疗的研究进展()
分享到62.8K

《医学研究与战创伤救治》（原医学研究生学报）[ISSN:1672-271X/CN:32-1713/R]

卷:
第21卷
期数:
2019年6期
页码:
625-630
栏目:
综述
出版日期:
2019-11-14

文章信息/Info

Title:
The research progress of immunotherapy in hepatocellular carcinoma
文章编号:
1672-271X（2019）06-0625-06
作者:
蒋伟;  李涛综述;  季国忠审校
210011 南京，南京医科大学第二附属医院消化内科
Author(s):
JIANG Wei;  LI Tao reviewing;  JI Guo-zhong checking
(Department of Gastroenterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu, China)
关键词:
原发性肝癌;  免疫治疗;  过继免疫细胞治疗;  免疫检查点抑制剂
Keywords:
hepatocellular carcinoma;  immunotherapy;  adoptive cell transfer therapy;  checkpoint inhibitor
分类号:
R735.7
DOI:
10.3969/j.issn.1672-271X.2019.06.016
文献标志码:
A
摘要:
原发性肝癌是我国最常见的恶性肿瘤之一。目前针对肝癌的传统治疗效果不佳，免疫治疗正在进行广泛的研究。肿瘤免疫治疗主要通过刺激机体产生特异性免疫反应，达到杀伤肿瘤细胞，控制肿瘤进展的目的。研究表明肝癌免疫疗法的应用在临床上已经产生了一定的成效，相信免疫疗法将逐渐成为肝癌治疗的一种新选择。文章主要就过继细胞转移治疗、免疫检查点治疗和肿瘤疫苗等肝癌的免疫疗法进行综述。
Abstract:
Hepatocellular carcinoma (HCC) is part of the most common malignant diseases in china. Traditional therapies for HCC only achieve limited therapeutic effects while immunotherapy is considered to be a new treatment option and has received widespread concern. Cancer immunotherapy targeting HCC can enhance the efficacy of the immune system and control the development of HCC. Decades of researches into cancer immunotherapy have yielded promising results which make it will become an optional therapy for HCC. Hence, we make a review about the adoptive cell transfer therapy, checkpoint inhibitor and tumor vaccines advances in the immunotherapy for HCC.

参考文献/References:

1 LiYW, YangFC, LuHQ, et al. Hepatocellular carcinoma and hepatitis B surface protein[J]. World J Gastroenterol, 2016, 22(6):1943-1952.
2 ChenW, ZhengR, ZhangS, et al. Cancer incidence and mortality in China, 2013[J]. Cancer Lett, 2017, 401:63-71.
3 季国忠，王静静. 细胞免疫及肠道益生菌治疗在肝癌治疗中的新进展[J]. 医学研究生学报, 2019, 32(7):673-677.
4 JuneCH, O’ConnorRS, KawalekarOU, et al. CAR T cell immunotherapy for human cancer[J]. Science, 2018, 359(6382):1361-1365.
5 van der StegenSJ, HamiehM, SadelainM. The pharmacology of second-generation chimeric antigen receptors[J]. Nat Rev Drug Discov, 2015, 14(7):499-509.
6 JensenMC, RiddellSR. Designing chimeric antigen receptors to effectively and safely target tumors[J]. Curr Opin Immunol, 2015, 33:9-15.
7 PegramHJ, PurdonTJ, van LeeuwenDG, et al. IL-12-secreting CD19-targeted cord blood-derived T cells for the immunotherapy of B-cell acute lymphoblastic leukemia[J]. Leukemia, 2015, 29(2):415-422.
8 TurtleCJ, HudecekM, JensenMC, et al. Engineered T cells for anti-cancer therapy[J]. Curr Opin Immunol, 2012, 24(5):633-639.
9 RestifoNP, DudleyME, RosenbergSA. Adoptive immunotherapy for cancer: harnessing the T cell response[J]. Nat Rev Immunol, 2012, 12(4):269-281.
10 李涛，蒋伟，季国忠，等. 嵌合抗原受体T细胞疗法治疗实体肿瘤的研究进展[J]. 医学研究生学报, 2019, 32(8):886-890.
11 BouattourM, RaymondE, QinS, et al. Recent developments of c-Met as a therapeutic target in hepatocellular carcinoma[J]. Hepatology,2018, 67(3):1132-1149.
12 GaoH, LiK, TuH, et al. Development of T cells redirected to glypican-3 for the treatment of hepatocellular carcinoma[J]. Clin Cancer Res,2014, 20(24):6418-6428.
13 ZhaiB, ShiDH, GaoH, et al. A phase I study of anti-GPC3 chimeric antigen receptor modified T cells (GPC3 CAR-T) in Chinese patients with refractory or relapsed GPC3 + hepatocellular carcinoma (r/r GPC3 + HCC) [J]. J Clin Oncol,35: 3049.
14 ChenC, LiK, JiangH, et al. Development of T cells carrying two complementary chimeric antigen receptors against glypican-3 and asialoglycoprotein receptor 1 for the treatment of hepatocellular carcinoma[J]. Cancer Immunol Immunother, 66(4):475-489.
15 GuoX, JiangH, ShiB, et al. Disruption of PD-1 Enhanced the Anti-tumor Activity of Chimeric Antigen Receptor T Cells Against Hepatocellular Carcinoma[J]. Front Pharmacol, 2018, 9:1118.
16 KrebsK, BottingerN, HuangLR, et al. T cells expressing a chimeric antigen receptor that binds hepatitis B virus envelope proteins control virus replication in mice[J]. Gastroenterology, 2013, 145(2):456-465.
17 LiuZ, FengZ, ZhuX, et al. Construction, expression, and characterization of an anti-tumor immunotoxin containing the human anti-c-Met single-chain antibody and PE38KDEL[J]. Immunol Lett, 2013, 149(1-2):30-40.
18 MuleJJ, ShuS, SchwarzSL, et al. Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2[J]. Science, 1984, 225(4669):1487-1489.
19 LotzeMT, MatoryYL, RaynerAA, et al. Clinical effects and toxicity of interleukin-2 in patients with cancer[J]. Cancer, 1986, 58(12):2764-2772.
20 KamiyaT, ChangYH, CampanaD: Expanded and Activated Natural Killer Cells for Immunotherapy of Hepatocellular Carcinoma[J]. Cancer Immunol Res, 2016, 4(7):574-581.
21 NishidaS, LeviDM, TzakisAG. Liver natural killer cell inoculum for liver transplantation with hepatocellular carcinoma[J]. Curr Opin Organ Transplant, 2013, 18(6):690-694.
22 VillanuevaMT. Immunotherapy: killing with natural killers, naturally[J]. Nat Rev Clin Oncol, 2014, 11(4):180.
23 YuM, LuoH, FanM, 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.
24 BrunnerSM, RubnerC, KesselringR, et al. Tumor-infiltrating, interleukin-33-producing effector-memory CD8(+) T cells in resected hepatocellular carcinoma prolong patient survival[J]. Hepatology, 2015, 61(6):1957-1967.
25 PanQZ, WangQJ, DanJQ, et al. A nomogram for predicting the benefit of adjuvant cytokine-induced killer cell immunotherapy in patients with hepatocellular carcinoma[J]. Sci Rep, 2015, 5:9202.
26 WangY, YangX, YuY, et al. Immunotherapy of patient with hepatocellular carcinoma using cytotoxic T lymphocytes ex vivo activated with tumor antigen-pulsed dendritic cells[J]. J Cancer, 2018, 9(2):275-287.
27 SangroB, Gomez-MartinC, de la MataM, et al. A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C[J]. J Hepatol, 2013, 59(1):81-88.
28 DuffyAG, UlahannanSV, Makorova-RusherO, et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma[J]. J Hepatol, 2017, 66(3):545-551.
29 徐成润，伍伟平. PD-1/PD-L1负性协同刺激通路在乙型病毒性肝炎慢性化中的地位及进展[J]. 东南国防医药, 2015,17(5):514-523.
30 SiderasK, BiermannK, VerheijJ, et al. PD-L1, Galectin-9 and CD8(+) tumor-infiltrating lymphocytes are associated with survival in hepatocellular carcinoma[J]. Oncoimmunology, 2017, 6(2):e1273309.
31 JungHI, JeongD, JiS, et al. Overexpression of PD-L1 and PD-L2 Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma[J]. Cancer Res Treat, 2017, 49(1):246-254.
32 Nivolumab Approved for Liver Cancer[J]. Cancer Discov, 2017, 7(11)OF3.
33 FisicaroP, ValdattaC, MassariM, et al. Antiviral intrahepatic T-cell responses can be restored by blocking programmed death-1 pathway in chronic hepatitis B[J]. Gastroenterology, 2010, 138(2):682-693.
34 El-KhoueiryAB, SangroB, YauT, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial[J]. Lancet,2017, 389(10088):2492-2502.
35 刘国印，冷楠楠，陈建民.Tim-3介导的免疫调节在类风湿性关节炎中的研究进展[J]. 东南国防医药, 2017, 19(4):385-389.
36 KikushigeY, AkashiK. TIM-3 as a therapeutic target for malignant stem cells in acute myelogenous leukemia[J]. Ann N Y Acad Sci, 2012, 1266:118-123.
37 PiaoYR, JinZH, YuanKC, et al. Analysis of Tim-3 as a therapeutic target in prostate cancer[J]. Tumour Biol, 2014, 35(11):10409-10414.
38 SakuishiK, ApetohL, SullivanJM, et al. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity[J]. J Exp Med, 2010, 207(10):2187-2194.
39 LiuJF, WuL, YangLL, et al. Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer[J]. J Exp Clin Cancer Res, 37(1):44.
40 FuSJ, QiCY, XiaoWK, et al. Glypican-3 is a potential prognostic biomarker for hepatocellular carcinoma after curative resection[J]. Surgery,2013, 154(3):536-544.
41 TsuchiyaN, YoshikawaT, FujinamiN, et al. Immunological efficacy of glypican-3 peptide vaccine in patients with advanced hepatocellular carcinoma[J]. Oncoimmunology, 2017, 6(10):e1346764.
42 SawadaY, YoshikawaT, OfujiK, et al. Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients[J]. Oncoimmunology, 2016, 5(5):e1129483.
43 BanchereauJ, SteinmanRM. Dendritic cells and the control of immunity[J]. Nature, 1998, 392(6673):245-252.
44 PalmerDH, MidgleyRS, MirzaN, et al. A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma[J]. Hepatology, 2009, 49(1):124-132.
45 BreitbachCJ, MoonA, BurkeJ, et al. A Phase 2, Open-Label, Randomized Study of Pexa-Vec (JX-594) Administered by Intratumoral Injection in Patients with Unresectable Primary Hepatocellular Carcinoma[J]. Methods Mol Biol, 2015, 1317:343-357.

相似文献/References:

[1]司 芩,钱晓莉,仝 威,等.实时超声造影对肝硬化背景下占位病变的鉴别诊断[J].医学研究与战创伤救治(原医学研究生学报),2009,11(02):121.
　SI Qin,QIAN Xiao-li,TONG Wei,et al.Differential diagnosis of focal hepatic cirrhosis lesions using real-time contrast-enhanced ultrasound[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2009,11(6):121.
[2]孙建军,马建芳,王晨光,等.综合介入治疗原发性肝癌长期存活34例[J].医学研究与战创伤救治(原医学研究生学报),2008,10(06):411.
　SUN Jian-jun,MA Jian-fang,WANG Chen-guang,et al.Clinical analysis of 34 cases of primary liver cancer survived for more than 5 years after comprehensive interventional therapy[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2008,10(6):411.
[3]倪 晶 综述,华海清 审校.索拉非尼联合中药治疗原发性肝癌的研究进展[J].医学研究与战创伤救治(原医学研究生学报),2015,17(02):175.[doi:10.3969/j.issn.1672-271X.2015.02.020]
[4]严海鸥,郝海燕,黄学芳,等.应对方式对原发性肝癌患者情绪和生活质量的影响[J].医学研究与战创伤救治(原医学研究生学报),2017,19(01):83.[doi:10.3969/j.issn.1672-271X.2017.01.023]
[5]沈兰超,张梅芹,许敏,等.华蟾素肝动脉推注联合化疗药物热灌注治疗原发性肝癌的临床价值[J].医学研究与战创伤救治(原医学研究生学报),2020,22(3):292.[doi:10.3969/j.issn.1672-271X.2020.03.015]

备注/Memo

备注/Memo:
收稿日期：2019-05-08
更新日期/Last Update: 2019-11-15