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自噬在肝细胞癌发生发展和免疫治疗调控中的作用及其机制

王沐淇 李亚萍 刘拉羊 党双锁 石娟娟 贾晓黎

引用本文:
Citation:

自噬在肝细胞癌发生发展和免疫治疗调控中的作用及其机制

DOI: 10.3969/j.issn.1001-5256.2019.05.045
基金项目: 

国家自然科学基金青年项目(31500650); 陕西省科学技术研究发展计划(2008K14-02); 

详细信息
  • 中图分类号: R735.7

Role and mechanism of autophagy in development and progression of hepatocellular carcinoma and regulation of immunotherapy

Research funding: 

 

  • 摘要: 自噬作为基础的生理现象,是维持细胞稳态和生理代谢的重要机制,还可以诱导细胞程序性死亡。目前大量研究证明,自噬在多种肿瘤的发生发展和演化过程中发挥重要作用,这为肿瘤的研究及治疗提供了新的思路。肝癌的发生机制极其复杂,其中免疫调控对肝癌发生、转移和侵袭的作用已经得到公认,近年来自噬被发现通过参与肿瘤免疫、氧化应激和维持细胞稳态等多方面影响肝癌进展,且可通过多种途径对肝癌免疫治疗效果产生影响。综述了自噬在肝癌发生发展和免疫治疗调控中的作用及其机制,以期深入了解自噬在肝癌中的重大影响和潜在的治疗价值。

     

  • [1] LIN H, YAN J, WANG Z, et al. Loss of immunity-supported senescence enhances susceptibility to hepatocellular carcinogenesis and progression in Toll-like receptor 2-deficient mice[J]. Hepatology, 2013, 57 (1) :171-182.
    [2] YU S, WANG Y, JING L, et al. Autophagy in the"inflammation-carcinogenesis"pathway of liver and HCC immunotherapy[J]. Cancer Lett, 2017, 411:82-89.
    [3] PENG JL, LAI X, WEI J. Dual role of autophagy in hepatitis B virus and related liver diseases[J]. J Clin Hepat, 2018, 34 (10) :2217-2220. (in Chinese) 彭佳丽, 赖欣, 韦嘉.自噬在HBV及相关肝脏疾病中的双重性作用[J].临床肝胆病杂志, 2018, 34 (10) :2217-2220.
    [4] EFEYAN A, COMB WC, SABATINI DM. Nutrient-sensing mechanisms and pathways[J]. Nature, 2015, 517 (7534) :302-310.
    [5] SIMONSEN A, TOOSE SA. Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes[J]. J Cell Biol, 2009, 186 (6) :773-782.
    [6] RUAN WJ, WAN FS. The role of Beclin1-Vps34 in the development of autophagy[J]. Chin J Cell Biol, 2016, 38 (11) :1420-1426. (in Chinese) 阮雯静, 万福生. Beclin1-Vps34在自噬发生发展中的作用[J].中国细胞生物学学报, 2016, 38 (11) :1420-1426.
    [7] ZHONG L, SHU W, DAI W, et al. Reactive oxygen speciesmediated c-Jun NH2-terminal kinase activation contributes to hepatitis B virus X protein-induced autophagy via regulation of the Beclin-1/Bcl-2 interaction[J]. J Virol, 2017, 91 (15) :e00001-17.
    [8] TAKAMURA A, KOMATSU M, HARA T, et al. Autophagydeficient mice develop multiple liver tumors[J]. Genes Dev, 2011, 25 (8) :795-800.
    [9] LEVINE B, KROEMER G. Autophagy in the pathogenesis of disease[J]. Cell, 2008, 132 (1) :27-42.
    [10] GALLUZZI L, PIETROCOLA F, BRAVO-SAN PEDRO JM, et al. Autophagy in malignant transformation and cancer progression[J]. EMBO J, 2015, 34 (7) :856-880.
    [11] WANG X, DENG Q, FENG K, et al. Insufficient radiofrequency ablation promotes hepatocellular carcinoma cell progression via autophagy and the CD133 feedback loop[J]. Oncol Rep, 2018, 40 (1) :241-251.
    [12] LI XP, CUI DL. Role of tumor microenvironment in hepatocellular carcinoma[J]. World Chin J Dig, 2014, 22 (9) :1219-1225. (in Chinese) 李小鹏, 崔东来.肿瘤微环境在肝细胞癌中的作用[J].世界华人消化杂志, 2014, 22 (9) :1219-1225.
    [13] FU S, FAN XG. Pathophysiological implications of hepatitis B X protein in tumor microenvironment of hepatocellular carcinoma[J]. World Chin J Dig, 2016, 24 (10) :1477-1484. (in Chinese) 付沙, 范学东. HBx在肿瘤微环境中的作用及其对肝癌发生发展的影响[J].世界华人消化杂志, 2016, 24 (10) :1477-1484.
    [14] ZHONG Z, SANCHEZ-LOPEZ E, KARIN M. Autophagy, inflammation, and immunity:A troika governing cancer and its treatment[J]. Cell, 2016, 166 (2) :288-298.
    [15] LIU B, FANG M, HU Y, et al. Hepatitis B virus X protein inhibits autophagic degradation by impairing lysosomal maturation[J]. Autophagy, 2014, 10 (3) :416-430.
    [16] SAITO T, ICHIMURA Y, TAGUCHI K, et al. p62/Sqstm1 promotes malignancy of HCV-positive hepatocellular carcinoma through Nrf2-dependent metabolic reprogramming[J]. Nat Commun, 2016, 7:12030.
    [17] LEVINE B, MIZUSHIMA N, VIRGIN HM. Autophagy in immunity and inflammation[J]. Nature, 2011, 469 (7330) :323-335.
    [18] SU WC, CHAO TC, HUANG YL, et al. Rab5 and class III phosphoinositide 3-kinase Vps34 are involved in hepatitis C virus NS4B-induced autophagy[J]. J Virol, 2011, 85 (20) :10561-10571.
    [19] OANA NA, THOMES PG, DONOHUE TM. Involvement of autophagy in alcoholic liver injury and hepatitis C pathogenesis[J]. World J Gastroenterol, 2011, 17 (20) :2507-2514.
    [20] AMIR M, CZAJA MJ. Autophagy in nonalcoholic steatohepatitis[J]. Expert Rev Gastroenterol Hepatol, 2011, 5 (2) :159-166.
    [21] SINGH R, KAUSHIK S, WANG Y, et al. Autophagy regulates lipid metabolism[J]. Nature, 2009, 458 (7242) :1131-1135.
    [22] SHALAPOUR S, KARIN M. Fatty acid-induced T cell loss greases liver carcinogenesis[J]. Cell Metab, 2016, 23 (5) :759-761.
    [23] DING WX, LI M, CHEN X, et al. Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice[J].Gastroenterology, 2010, 139 (5) :1740-1752.
    [24] WU D, WANG X, ZHOU R, et al. Alcohol steatosis and cytotoxicity:the role of cytochrome P4502E1 and autophagy[J].Free Radic Biol Med, 2012, 53 (6) :1346-1357.
    [25] WANG LR, ZHU GQ, SHI KQ, et al. Autophagy in ethanolexposed liver disease[J]. Expert Rev Gastroenterol Hepatol, 2015, 9 (8) :1031-1037.
    [26] KOMATSU M, WAGURI S, UENO T, et al. Impairment of starvation induced and constitutive autophagy in Atg7-deficient mice[J]. J Cell Biol, 2005, 169 (3) :425-434.
    [27] INAMI Y, WAGURI S, SAKAMOTO A, et al. Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells[J].J Cell Biol, 2011, 193 (2) :275-284.
    [28] BAO L, CHANDRA PK, MOROZ K, et al. Impaired autophagy response in human hepatocellular carcinoma[J]. Exp Mol Pathol, 2014, 96 (2) :149-154.
    [29] DUFFY A, LE J, SAUSVILLE E, et al. Autophagy modulation:a target for cancer treatment development[J]. Cancer Chemother Pharmacol, 2015, 75 (3) :439-447.
    [30] HEN W, MA T, SHEN XN, et al. Macrophage-induced tumor angiogenesis is regulated by the TSC2-m TOR pathway[J].Cancer Res, 2012, 72 (6) :1363-1372.
    [31] BOTBOL Y, GUERRERO-ROS I, MACIAN F, et al. Key roles of autophagy in regulating T-cell function[J]. Eur J Immunol, 2016, 46 (6) :1326-1334.
    [32] MILLER BC, ZHAO Z, STEPHENSON LM, et al. The autophagy gene ATG5 plays an essential role in B lymphocyte development[J]. Autophagy, 2008, 4 (3) :309-314.
    [33] HAHN T, AKPORIAYE ET. alpha-TEA as a stimulator of tumor autophagy and enhancer of antigen cross-presentation[J]. Autophagy, 2013, 9 (3) :429-431.
    [34] SUN K, XU L, JING Y, et al. Autophagy-deficient Kupffer cells promote tumorigenesis by enhancing mtROS-NF-κBIL1α/β-dependent inflammation and fibrosis during the preneoplastic stage of hepatocarcinogenesis[J]. Cancer Lett, 2017, 388:198-207.
    [35] MAH LY, RYAN KM. Autophagy and cancer[J]. Cold Spring Harb Perspect Biol, 2012, 4 (1) :a008821.
    [36] LI P, DU Q, CAO Z, et al. Interferon-gamma induces autophagy with growth inhibition and cell death in human hepatocellular carcinoma (HCC) cells through interferon-regulatory factor-1[J]. Cancer Lett, 2012, 314 (2) :213-222.
    [37] TIAN Y, KUO CF, SIR D, et al. Autophagy inhibits oxidative stress and tumor suppressors to exert its dual effect on hepatocarcinogenesis[J]. Cell Death Differ, 2015, 22 (6) :1025-1034.
    [38] GUO JY, XIA B, WHITE E. Autophagy-mediated tumor promotion[J]. Cell, 2013, 155 (6) :1216-1219.
    [39] YANG X, YU DD, YAN F, et al. The role of autophagy induced by tumor microenvironment in different cells and stages of cancer[J]. Cell Biosci, 2015, 5:14.
    [40] WU DH, JIA CC, CHEN J, et al. Autophagic LC3B overexpression correlates with malignant progression and predicts a poor prognosis in hepatocellular carcinoma[J]. Tumour Biol, 2014, 35 (12) :12225-12233.
    [41] YUAN H, LI AJ, MA SL, et al. Inhibition of autophagy significantly enhances combination therapy with sorafenib and HDAC inhibitors for human hepatoma cells[J]. World J Gastroenterol, 2014, 20 (17) :4953-4962.
    [42] SONG B, QI B, CHENG HS, et al. Ulinastatin reduces the resistance of liver cancer cells to epirubicin by inhibiting autophagy[J]. PLo S One, 2015, 10 (3) :e0120694.
    [43] SHIBUTANI ST, SAITOH T, NOWAG H, et al. Autophagy and autophagy-related proteins in the immune system[J]. Nat Immunol, 2015, 16 (10) :1014-1024.
    [44] PAN H, CHEN L, XU Y, et al. Autophagy-associated immune responses and cancer immunotherapy[J]. Oncotarget, 2016, 7 (16) :21235-21246.
    [45] GABAI VL, SHIFRIN VI. Feasibility analysis of p62 (SQSTM1) -encoding DNA vaccine as a novel cancer immunotherapy[J]. Int Rev Immunol, 2014, 33 (5) :375-382.
    [46] LI H, LI X, LIU S, et al. Programmed cell death-1 (PD-1) checkpoint blockade in combination with a mammalian target of rapamycin inhibitor restrains hepatocellular carcinoma growth induced by hepatoma cell-intrinsic PD-1[J]. Hepatology, 2017, 66 (6) :1920-1933.
    [47] EL-KHOUEIRY AB, SANGRO B, YAU H, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate040) :An open-label, non-comparative, phase 1/2 dose escalation and expansion trial[J]. Lancet, 2017, 389 (10088) :2492-2502.
    [48] KUDO M. Immuno-oncology in hepatocellular carcinoma:2017 Update[J]. Oncology, 2017, 93 (Suppl 1) :147-159.
    [49] REN ZG. Immunotherapy for hepatocellular carcinoma[J]. J Clin Hepat, 2018, 34 (7) :1371-1373. (in Chinese) 任志刚.肝细胞癌的免疫治疗[J].临床肝胆病杂志, 2018, 34 (7) :1371-1373.
    [50] LOPEZ-SOTO A, BRAVO-SAN PEDRO JM, KROEMER G, et al. Involvement of autophagy in NK cell development and function[J]. Autophagy, 2017, 13 (3) :633-636.
    [51] LEE JH, LIM YS, YEON JE, et al. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma[J]. Gastroenterology, 2015, 148 (7) :1383-1391.
    [52] JIANG SS, TANG Y, ZHANG YJ, et al. A phase I clinical trial utilizing autologous tumor-infiltrating lymphocytes in patients with primary hepatocellular carcinoma[J]. Oncotarget, 2015, 6 (38) :41339-41349.
    [53] WANG Y, TANG Y, ZHANG YJ, et al. CD133-directed CAR T cells for advanced metastasis malignancies:A phase I trial[J]. Oncoimmunology, 2018, 7 (7) :e1440169.
    [54] GABAI VL, SHIFRIN VI. Feasibility analysis of p62 (SQSTM1) -encoding DNA vaccine as a novel cancer immunotherapy[J]. Int Rev Immunol, 2014, 33 (5) :375-382.
    [55] 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.
    [56] YAN Y, LIU N, LIU L, et al. Autophagy enhances antitumor immune responses induced by irradiated hepatocellular carcinoma cells engineered to express hepatitis B virus X protein[J]. Oncol Rep, 2013, 30 (2) :993-999.
    [57] WANG S, ZHU M, WANG Q, et al. Alpha-fetoprotein inhibits autophagy to promote malignant behaviour in hepatocellular carcinoma cells by activating PI3K/AKT/m TOR signalling[J].Cell Death Dis, 2018, 9 (10) :1027.
    [58] NAKAGAWA H, MIZUKOSHI E, KOBAYASHI E, et al. Association between high-avidity T-cell receptors, induced by alpha-fetoprotein-derived peptides, and anti-tumor effects in patients with hepatocellular carcinoma[J]. Gastroenterology, 2017, 152 (6) :1395-1406. e1310.
    [59] YUAN S, FANG X, XU Y, et al. An oncolytic adenovirus that expresses the HAb18 and interleukin 24 genes exhibits enhanced antitumor activity in hepatocellular carcinoma cells[J].Oncotarget, 2016, 7 (37) :60491-60502.
    [60] ZHANG J, LAI W, LI Q, et al. A novel oncolytic adenovirus targeting Wnt signaling effectively inhibits cancer-stem like cell growth via metastasis, apoptosis and autophagy in HCC models[J]. Biochem Biophys Res Commun, 2017, 491 (2) :469-477.
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  • 收稿日期:  2018-10-24
  • 出版日期:  2019-05-20
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