肝细胞癌细胞免疫治疗的研究进展

张野; 张明杰; 贾战生

doi:10.3969/j.issn.1001-5256.2014.09.006

肝细胞癌细胞免疫治疗的研究进展

DOI: 10.3969/j.issn.1001-5256.2014.09.006

1. 第四军医大学唐都医院感染病·肝病中心

详细信息

中图分类号: R735.7
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出版历程
- 收稿日期: 2014-07-30
- 出版日期: 2014-09-20

Research advances in cellular immunotherapy for primary hepatocellular carcinoma

Center of Infectious Diseases and Liver Diseases, Tangdu Hospital, Fourth Military Medical University

摘要

摘要: 肝细胞癌(HCC)的治疗目前主要采用以手术为主、配合局部放疗和化疗的综合治疗措施,但多数患者经综合治疗后也容易复发,缺乏有效的治疗药物和手段,总体治疗效果并不理想。越来越多的证据表明,肝癌的发生、发展、转移和复发与机体免疫系统有密切的关系。因此,免疫治疗特别是细胞免疫治疗可以调节机体免疫功能,诱导特异性肿瘤免疫,达到治疗肝癌、减少肝癌复发和转移的目的,已成为肝癌综合治疗的重要组成部分。对细胞免疫治疗在HCC中的临床前研究和临床试验取得的成果进行综述,并讨论当前存在的问题。
- 癌,肝细胞 /
- 免疫疗法,主动 /
- 免疫疗法,过继 /
- 综述
Abstract: The present therapy for primary hepatocellular carcinoma ( HCC) consists of surgery as well as local radiotherapy and chemotherapy. However, the majority of patients are susceptible to recurrence after comprehensive treatment, and the overall treatment outcome is not ideal due to the lack of effective drugs and strategies. Increasing evidence has demonstrated that the immune system is closely related to the development, progression, metastasis, and recurrence of HCC. Thus, immune therapy, especially cellular immunotherapy, could regulate immune function and induce specific antitumor immunity to achieve the goal of controlling HCC and reducing its recurrence and metastasis, which has become an essential part in the comprehensive treatment of HCC. The findings in preclinical and clinical studies on cellular immunotherapy for HCC data are reviewed, and the current problems are discussed.
- carcinoma, hepatocellular /
- immunotherapy, active /
- immunotherapy, adoptive /
- review

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参考文献(32)

[1] CHEN JG, ZHANG SW.Liver cancer epidemic in China:past, present and future[J].Semin Cancer Biol, 2011, 21 (1) :59-69.

[2] LLOVET JM, BURROUGHS A, BRUIX J.Hepatocellular carcinoma[J].Lancet, 2003, 362 (9399) :1907-1917.

[3]LLOVET JM, RICCI S, MAZZAFERRO V, et al.Sorafenib in advanced hepatocellular carcinoma[J].N Engl J Med, 2008, 359 (4) :378-390.

[4]MORIMOTO M, NUMATA K, KONDO M, et al.Higher discontinuation and lower survival rates are likely in elderly Japanese patients with advanced hepatocellular carcinoma receiving sorafenib[J].Hepatol Res, 2011, 41 (4) :296-302.

[5]PALUCKA K, BANCHEREAU J.Cancer immunotherapy via dendritic cells[J].Nat Rev Cancer, 2012, 12 (4) :265-277.

[6] BRAY SM, VUJANOVIC L, BUTTERFIELD LH.Dendritic cellbased vaccines positively impact natural killer and regulatory T cells in hepatocellular carcinoma patients[J].Clin Dev Immunol, 2011, 2011:249281.

[7] ELANSARY M, MOGAWER S, ELHAMID SA, et al.Immunotherapy by autologous dendritic cell vaccine in patients with advanced HCC[J].J Cancer Res Clin Oncol, 2013, 139 (1) :39-48.

[8] CABILLIC F, TOUTIRAIS O, LAVOUV, et al.Aminobisphosphonate-pretreated dendritic cells trigger successful Vgamma9Vdelta2 T cell amplification for immunotherapy in advanced cancer patients[J].Cancer Immunol Immunother, 2010, 59 (11) :1611-1619.

[9] NAKAMOTO Y, MIZUKOSHI E, KITAHARA M, et al.Prolonged recurrence-free survival following OK432-stimulated dendritic cell transfer into hepatocellular carcinoma during transarterial embolization[J].Clin Exp Immunol, 2011, 163 (2) :165-177.

[10] GE C, XING Y, WANG Q, et al.Improved efficacy of therapeutic vaccination with dendritic cells pulsed with tumor cell lysate against hepatocellular carcinoma by introduction of 2 tandem repeats of microbial HSP70 peptide epitope 407-426 and OK-432[J].Int Immunopharmacol, 2011, 11 (12) :2200-2207.

[11] YANG X, ZHU H, HU Z.Dendritic cells transduced with TEM8 recombinant adenovirus prevents hepatocellular carcinoma angiogenesis and inhibits cells growth[J].Vaccine, 2010, 28 (43) :7130-7135.

[12] PENG W, ZHAO G, MA Y, et al.Dendritic cells transfected with PEG10 recombinant adenovirus elicit anti-tumor immune response in vitro and in vivo[J].Vaccine, 2011, 29 (18) :3501-3506.

[13] CHEN Y, HUANG A, GAO M, et al.Potential therapeutic value of dendritic cells loaded with NYESO1 protein for the immunotherapy of advanced hepatocellular carcinoma[J].Int J Mol Med, 2013, 32 (6) :1366-1372.

[14]SU S, ZHOU H, XUE M, et al.Anti-tumor efficacy of a hepatocellular carcinoma vaccine based on dendritic cells combined with tumor-derived autophagosomes in murine models[J].Asian Pac J Cancer Prev, 2013, 14 (5) :3109-3116.

[15] TADA F, ABE M, HIROOKA M, et al.Phase I/II study of immunotherapy using tumor antigen-pulsed dendritic cells in patients with hepatocellular carcinoma[J].Int J Oncol, 2012, 41 (5) :1601-1609.

[16]BIRON CA.Expansion, maintenance, and memory in NK and T cells during viral infections:responding to pressures for defense and regulation[J].PLoS Pathog, 2010, 6 (3) :e1000816.

[17]CHENG M, ZHI K, GAO X, et al.Activation of cellular immunity and marked inhibition of liver cancer in a mouse model following gene therapy and tumor expression of GM-SCF, IL-21, and Rae-1[J].Mol Cancer, 2013, 12 (1) :166.

[18]SPRINZL MF, REISINGER F, PUSCHNIK A, et al.Sorafenib perpetuates cellular anticancer effector functions by modulating the crosstalk between macrophages and natural killer cells[J].Hepatology, 2013, 57 (6) :2358-2368.

[19]NISHIDA S, LEVI DM, TZAKIS AG.Liver natural killer cell inoculum for liver transplantation with hepatocellular carcinoma[J].Curr Opin Organ Transplant, 2013, 18 (6) :690-694.

[20]JIANG W, ZHANG C, TIAN Z, et al.hIFN-αgene modification augments human natural killer cell line anti-human hepatocellular carcinoma function[J].Gene Ther, 2013, 20 (11) :1062-1069.

[21]KAWATA A, UNE Y, HOSOKAWA M, et al.Adjuvant chemoimmunotherapy for hepatocellular carcinoma patients.Adriamycin, interleukin-2, and lymphokine-activated killer cells versus adriamycin alone[J].Am J Clin Oncol, 1995, 18 (3) :257-262.

[22]PU LY, PANG RL, JIN YH, et al.Effects of hepatic artery chemotherapeutic embolization combined with perfusing LAK cells into hepatic artery after radical operation of liver cancer[J].Chin J Hepatol, 2000, 8 (3) :142-143. (in Chinese) 镤利宇, 庞瑞麟, 金银慧, 等.肝癌根治性切除术后肝动脉化疗栓塞联合LAK细胞肝动脉灌注的价值[J].中华肝脏病杂志, 2000, 8 (3) :142-143.

[23]TAKAYAMA T, MAKUUCHI M, SEKINE T, et al.Distribution and therapeutic effect of intraarterially transferred tumor-infiltrating lymphocytes in hepatic malignancies.A preliminary report[J].Cancer, 1991, 68 (11) :2391-2396.

[24] TAKAYAMA T, SEKINE T, MAKUUCHI M, et al.Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma:a randomised trial[J].Lancet, 2000, 356 (9232) :802-807.

[25]WANG FS, LIU MX, ZHANG B, et al.Antitumor activities of human autologous cytokine-induced killer (CIK) cells against hepatocellular carcinoma cells in vitro and in vivo[J].World J Gastroenterol, 2002, 8 (3) :464-468.

[26] PAN K, LI YQ, WANG W, et al.The efficacy of cytokine-induced killer cell infusion as an adjuvant therapy for postoperative hepatocellular carcinoma patients[J].Ann Surg Oncol, 2013, 20 (13) :4305-4311.

[27]WANG XP, XU M, GAO HF, et al.Intraperitoneal perfusion of cytokine-induced killer cells with local hyperthermia for advanced hepatocellular carcinoma[J].World J Gastroenterol, 2013, 19 (19) :2956-2962.

[28]HUANG ZM, LI W, LI S, et al.Cytokine-induced killer cells in combination with transcatheter arterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma patients[J].J Immunother, 2013, 36 (5) :287-293.

[29] LI X, DAI D, SONG X, et al.A meta-analysis of cytokine-induced killer cells therapy in combination with minimally invasive treatment for hepatocellular carcinoma[J].Clin Res Hepatol Gastroenterol, 2014.[Epub ahead of print]

[30]LEE K, HWANG H, NAM KT.Immune response and the tumor microenvironment:how they communicate to regulate gastric cancer[J].Gut Liver, 2014, 8 (2) :131-139.

[31]ALTOMONTE J, EBERT O.Sorting out pandora's box:discerning the dynamic roles of liver microenvironment in oncolytic virus therapy for hepatocellular carcinoma[J].Front Oncol, 2014, 4:85.

[32]WILLIMSKY G, PROTZER U, KNOLLE P, et al.Adoptive Tcell therapy to treat liver cancer:is the liver microenvironment key?[J].Oncotarget, 2013, 4 (8) :1117-1118.引证本文:ZHANG Y, ZHANG MJ, JIA ZS.Research advances in cellular immunotherapy for primary hepatocellular carcinoma[J].J Clin Hepatol, 2014, 30 (9) :860-864. (in Chinese) 张野, 张明杰, 贾战生.肝细胞癌细胞免疫治疗的研究进展[J].临床肝胆病杂志, 2014, 30 (9) :860-864.

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