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基于PD-1/PD-L1信号通路的肝棘球蚴病免疫逃逸研究
DOI: 10.3969/j.issn.1001-5256.2023.01.034
利益冲突声明：所有作者均声明不存在利益冲突。
作者贡献声明：杨康洁负责资料分析和撰写论文；鄂维建参与收集资料和修改论文；芦永良负责指导撰写文章并最后定稿。
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摘要: PD-1/PD-L1共同组成适应性免疫反应的刺激信号通路，现已被广泛应用于肿瘤免疫逃逸机制及肿瘤治疗的研究中。同时，其信号通路也被证实与肝棘球蚴病的免疫逃逸有密切联系。本文回顾了PD-1和PD-L1的化学结构及其信号通路的作用机理，综述了PD-1/PD-L1信号通路在肝棘球蚴病免疫逃逸中的作用，即PD-1/PD-L1信号通路在三种理论下参与肝棘球蚴病的免疫逃逸，以期从新的角度探讨肝棘球蚴病的免疫逃逸，为肝棘球蚴病的诊断和治疗提供依据和思路。Abstract: PD-1 and PD-L1 together constitute the stimulus signaling pathway of adaptive immune response, which has been widely used in the research on the mechanism of tumor immune escape and tumor therapy. At the same time, its signaling pathway has been proved to be closely associated with the immune escape of hepatic echinococcosis. This article reviews the chemical structures of PD-1 and PD-L1, the mechanism of the PD-1/PD-L1 signaling pathway, and the role of the PD-1/PD-L1 signaling pathway in immune escape of hepatic echinococcosis, i.e., the PD-1/PD-L1 signaling pathway is involved in immune escape of hepatic echinococcosis under three theories, so as to explore the immune escape of hepatic echinococcosis from a new perspective and provide a basis and ideas for the diagnosis and treatment of hepatic echinococcosis.
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Key words:
- Echinococcosis, Hepatic /
- Programmed Death 1 /
- PD-1 Ligand /
- Tumor Escape
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图 1 PD-1/PD-L1信号通路作用机制简图
Figure 1. Schematic diagram of action mechanism of PD-1/PD-L1 signaling pathway
表 1 目前PD-1/PD-L1信号通路参与肝棘球蚴病的免疫逃逸理论
Table 1. Current immune escape theory of the involvement of PD-1/PD-L1 signaling pathway in hepatic echinococcosis
免疫逃逸理论 PD-1/PD-L1信号通路参与过程 Th1/Th2失衡理论 PD-1/PD-L1信号通路介导使Th2增多，Th1减少。适应性免疫应答向Th2反应偏移 Th17/Treg失衡理论 PD-1/PD-L1信号通路介导使细胞因子IL-17分泌减少，IL-17/IL-10和RORγt/Foxp3比值降低，适应性免疫应答向Treg偏移 能量失衡理论 PD-1/PD-L1信号通路通过拮抗PI3K/AKT通路和mTOR信号通路，偏移免疫应答，导致免疫细胞能量补给不足 
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[1] WEN H, VUITTON L, TUXUN T, et al. Echinococcosis: Advances in the 21st Century[J]. Clin Microbiol Rev, 2019, 32(2): e00075-18. DOI: 10.1128/CMR.00075-18. [2] SEN P, DEMIRDAL T, NEMLI SA. Evaluation of clinical, diagnostic and treatment aspects in hydatid disease: analysis of an 8-year experience[J]. Afr Health Sci, 2019, 19(3): 2431-2438. DOI: 10.4314/ahs.v19i3.17. [3] MCMANUS DP, GRAY DJ, ZHANG W, et al. Diagnosis, treatment, and management of echinococcosis[J]. BMJ, 2012, 344: e3866. DOI: 10.1136/bmj.e3866. [4] MINAEV SV, GERASIMENKO IN, KIRGIZOV IV, et al. Laparoscopic treatment in children with hydatid cyst of the liver[J]. World J Surg, 2017, 41(12): 3218-3223. DOI: 10.1007/s00268-017-4129-x. [5] LIU GH, YANG JY, TANG MJ. Research progress on the pathogenesis of human hepatic echinococcosis[J]. Chin J Zoonos, 2021, 37(2): 165-170. DOI: 10.3969/j.issn.1002-2694.2020.00.156.刘光辉, 杨金煜, 唐明杰. 人肝细粒棘球蚴病致病的研究进展[J]. 中国人兽共患病学报, 2021, 37(2): 165-170. DOI: 10.3969/j.issn.1002-2694.2020.00.156. [6] YIN LL, SHU LS. Research progress of PD-L1/PD-1 pathway in cervical cancer[J]. J Med Res, 2018, 47(7): 13-16, 20. https://www.cnki.com.cn/Article/CJFDTOTAL-YXYZ201807006.htm殷林林, 舒丽莎. PD-L1/PD-1通路在宫颈癌中的研究进展[J]. 医学研究杂志, 2018, 47(7): 13-16, 20. https://www.cnki.com.cn/Article/CJFDTOTAL-YXYZ201807006.htm [7] ISHIDA Y, AGATA Y, SHIBAHARA K, et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death[J]. EMBO J, 1992, 11(11): 3887-3895. DOI: 10.1002/j.1460-2075.1992.tb05481.x. [8] HAN Y, LIU D, LI L. PD-1/PD-L1 pathway: current researches in cancer[J]. Am J Cancer Res, 2020, 10(3): 727-742. [9] TERME M, ULLRICH E, AYMERIC L, et al. IL-18 induces PD-1-dependent immunosuppression in cancer[J]. Cancer Res, 2011, 71(16): 5393-5399. DOI: 10.1158/0008-5472.CAN-11-0993. [10] ZHONG YM, WU F, LUO XC, et al. Mechanism of moxibustion in the treatment of rheumatoid arthritis based on PD-1/PD-L1 signaling pathway[J]. Chin Acupunct Moxibust, 2020, 40(9): 976-982. DOI: 10.13703/j.0255-2930.20190729-0002.钟玉梅, 吴菲, 罗小超, 等. 基于PD-1/PD-L1信号通路艾灸治疗类风湿性关节炎的机制研究[J]. 中国针灸, 2020, 40(9): 976-982. DOI: 10.13703/J.0255-2930.20190729-0002. [11] RIELLA LV, PATERSON AM, SHARPE AH, et al. Role of the PD-1 pathway in the immune response[J]. Am J Transplant, 2012, 12(10): 2575-2587. DOI: 10.1111/j.1600-6143.2012.04224.x. [12] PATSOUKIS N, WANG Q, STRAUSS L, et al. Revisiting the PD-1 pathway[J]. Sci Adv, 2020, 6(38): eabd2712. DOI: 10.1126/sciadv.abd2712. [13] GIANCHECCHI E, DELFINO DV, FIERABRACCI A. Recent insights into the role of the PD-1/PD-L1 pathway in immunological tolerance and autoimmunity[J]. Autoimmun Rev, 2013, 12(11): 1091-1100. DOI: 10.1016/j.autrev.2013.05.003. [14] LI H, XU YX, DU XH. Research progress of PD-1/PD-L1 signaling pathway and its antibody in tumor immunotherapy[J]. Chin J Cell Mol Immunol, 2016, 32(8): 1144-1147. https://www.cnki.com.cn/Article/CJFDTOTAL-XBFM201608031.htm李浩, 徐迎新, 杜晓辉. PD-1/PD-L1信号通路及其抗体在肿瘤免疫治疗中的研究进展[J]. 细胞与分子免疫学杂志, 2016, 32(8): 1144-1147. https://www.cnki.com.cn/Article/CJFDTOTAL-XBFM201608031.htm [15] YAO H, HOU YX, REN JH, et al. The effect of hualangin on apoptosis of HepG2 cells based on PI3K/Akt signaling pathway[J]. Chin J Exp Med Formul, 2022, 28(9): 80-87. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSFX202209012.htm姚红, 侯宇芯, 任晋宏, 等. 基于PI3K/Akt信号通路探讨华良姜素抗肝癌细胞HepG2凋亡的作用机制[J]. 中国实验方剂学杂志, 2022, 28(9): 80-87. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSFX202209012.htm [16] IWAI Y, ISHIDA M, TANAKA Y, et al. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade[J]. Proc Natl Acad Sci U S A, 2002, 99(19): 12293-12297. DOI: 10.1073/pnas.192461099. [17] PÓPULO H, LOPES JM, SOARES P. The mTOR signalling pathway in human cancer[J]. Int J Mol Sci, 2012, 13(2): 1886-1918. DOI: 10.3390/ijms13021886. [18] MARASCO M, BERTEOTTI A, WEYERSHAEUSER J, et al. Molecular mechanism of SHP2 activation by PD-1 stimulation[J]. Sci Adv, 2020, 6(5): eaay4458. DOI: 10.1126/sciadv.aay4458. [19] GRONER B, von MANSTEIN V. Jak Stat signaling and cancer: Opportunities, benefits and side effects of targeted inhibition[J]. Mol Cell Endocrinol, 2017, 451: 1-14. DOI: 10.1016/j.mce.2017.05.033. [20] HUANG C, BAI L. PD-1/PD-L1 signaling pathway and tumor immune escape[J]. Curr Immunol, 2020, 40(4): 329-333, 340. https://www.cnki.com.cn/Article/CJFDTOTAL-SHMY202004013.htm黄聪, 白丽. PD-1/PD-L1信号通路与肿瘤免疫逃逸[J]. 现代免疫学, 2020, 40(4): 329-333, 340. https://www.cnki.com.cn/Article/CJFDTOTAL-SHMY202004013.htm [21] DUGUM M, HANOUNEH I, LOPEZ R, et al. Hepatocellular carcinoma in the setting of chronic hepatitis B virus infection: tumor recurrence and survival rates after liver transplantation[J]. Transplant Proc, 2015, 47(6): 1939-1944. DOI: 10.1016/j.transproceed.2015.02.021. [22] ENDO M, YAMAMOTO H, SETSU N, et al. Prognostic significance of AKT/mTOR and MAPK pathways and antitumor effect of mTOR inhibitor in NF1-related and sporadic malignant peripheral nerve sheath tumors[J]. Clin Cancer Res, 2013, 19(2): 450-461. DOI: 10.1158/1078-0432.CCR-12-1067. [23] HUI E, CHEUNG J, ZHU J, et al. T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition[J]. Science, 2017, 355(6332): 1428-1433. DOI: 10.1126/science.aaf1292. [24] THIBULT ML, MAMESSIER E, GERTNER-DARDENNE J, et al. PD-1 is a novel regulator of human B-cell activation[J]. Int Immunol, 2013, 25(2): 129-137. DOI: 10.1093/intimm/dxs098. [25] LI WT, TU J, YANG W. Research progress of PD-L1/PD-1 signaling pathway in immune mechanism of sepsis[J]. Acta Med Univ Sci Technol Huazhong, 2017, 46(2): 237-240. DOI: 10.3870/j.issn.1672-0741.2017.02.025.李文甜, 涂计, 杨闻. PD-L1/PD-1信号通路在脓毒血症的免疫机制中的研究进展[J]. 华中科技大学学报(医学版), 2017, 46(2): 237-240. DOI: 10.3870/j.issn.1672-0741.2017.02.025. [26] JIANG HY, ZHANG YQ. Research progress of hepatic alveolar echinococcosis and its mechanism of immune escape[J/CD]. J Clin Pharm Literat Electr, 2019, 6(61): 183.姜宏猷, 张易青. 肝泡型包虫病及其免疫逃逸机制研究进展[J/CD]. 临床医药文献电子杂志, 2019, 6(61): 183. [27] ZHANG LS, YUAN LG. Study on immune escape mechanism of Echinococcosis granulosus[J]. Sci Technol Inform Anim Husb Veterin Sci, 2020, 6: 15. DOI: 10.3969/J.ISSN.1671-6027.2020.06.008.张林生, 袁莉刚. 细粒棘球蚴病的免疫逃逸机制研究[J]. 畜牧兽医科技信息, 2020, 6: 15. DOI: 10.3969/J.ISSN.1671-6027.2020.06.008. [28] LIU HD, WANG HB, FAN HN, et al. Immune evasion mechanism of alveolar echinococcosis[J]. Chin J Parasitol Parasitic Dis, 2018, 36(6): 655-660. https://www.cnki.com.cn/Article/CJFDTOTAL-ZJSB201806024.htm刘寒冬, 王宏宾, 樊海宁, 等. 多房棘球蚴病的免疫逃避机制[J]. 中国寄生虫学与寄生虫病杂志, 2018, 36(6): 655-660. https://www.cnki.com.cn/Article/CJFDTOTAL-ZJSB201806024.htm [29] SPEISER DE, UTZSCHNEIDER DT, OBERLE SG, et al. T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?[J]. Nat Rev Immunol, 2014, 14(11): 768-774. DOI: 10.1038/nri3740. [30] XIN Y, ZHANG FB, LI YH, et al. Changes of soluble Tim3/Galectin9 in serum of patients with echinococcosis[J]. J Immunol, 2014, 30(10): 910-913. https://www.cnki.com.cn/Article/CJFDTOTAL-MYXZ201410016.htm辛燕, 张峰波, 李艳华, 等. 棘球蚴病患者血清中可溶性Tim3/Galectin9的变化[J]. 免疫学杂志, 2014, 30(10): 910-913. https://www.cnki.com.cn/Article/CJFDTOTAL-MYXZ201410016.htm [31] YU XD, YE JR. The role of TH17/TREG imbalance in hydatid induced allergic reaction[J]. Mod Immunol, 2020, 40(1): 81-85. https://www.cnki.com.cn/Article/CJFDTOTAL-SHMY202001015.htm于晓东, 叶建荣. TH17/TREG失衡在包虫所致过敏反应中作用的研究进展[J]. 现代免疫学, 2020, 40(1): 81-85. https://www.cnki.com.cn/Article/CJFDTOTAL-SHMY202001015.htm [32] NEWPORT MJ, FINAN C. Genome-wide association studies and susceptibility to infectious diseases[J]. Brief Funct Genom, 2011, 10(2): 98-107. DOI: 10.1093/bfgp/elq037. [33] MOURGLIA-ETTLIN G, MARQUÉS JM, CHABALGOITY JA, et al. Early peritoneal immune response during Echinococcus granulosus establishment displays a biphasic behavior[J]. PLoS Negl Trop Dis, 2011, 5(8): e1293. DOI: 10.1371/journal.pntd.0001293. [34] LI YH, WANG J, HU XA, et al. Changes of soluble PD-1/PD-L1 and related cytokines in patients with echinococcosis[J]. Chin J Cell Mol Immunol, 2014, 30(4): 421-423. https://www.cnki.com.cn/Article/CJFDTOTAL-XBFM201404024.htm李艳华, 王晶, 胡晓安, 等. 棘球蚴病患者血清中可溶性PD-1/PD-L1与相关细胞因子的水平变化[J]. 细胞与分子免疫学杂志, 2014, 30(4): 421-423. https://www.cnki.com.cn/Article/CJFDTOTAL-XBFM201404024.htm [35] SONG XT, ZHU P, LONG S, et al. Study on immune escape mechanism of echinococcosis granulosus[J]. J Pract Hosp Clin, 2017, 14(3): 138-141. DOI: 10.3969/j.issn.1672-6170.2017.03.048.宋旭彤, 朱鹏, 龙爽, 等. 细粒棘球蚴病的免疫逃逸机制探讨[J]. 实用医院临床杂志, 2017, 14(3): 138-141. DOI: 10.3969/j.issn.1672-6170.2017.03.048. [36] LA X, ZHANG F, LI Y, et al. Upregulation of PD-1 on CD4+CD25+T cells is associated with immunosuppression in liver of mice infected with Echinococcus multilocularis[J]. Int Immunopharmacol, 2015, 26(2): 357-366. DOI: 10.1016/j.intimp.2015.04.013. [37] PAN SY, WANG ZX, ZHOU Y, et al. The function and mechanism of PD-1/PD-L1 signaling pathway in liver diseases[J]. J Clin Hepatol, 2019, 35(3): 672-676. DOI: 10.3969/j.issn.1001-5256.2019.03.050.潘思宇, 王志鑫, 周灜, 等. PD-1/PD-L1信号通路在肝脏疾病中的功能及作用机制[J]. 临床肝胆病杂志, 2019, 35(3): 672-676. DOI: 10.3969/j.issn.1001-5256.2019.03.050. [38] ZHENG H, ZHANG W, ZHANG L, et al. The genome of the hydatid tapeworm Echinococcus granulosus[J]. Nat Genet, 2013, 45(10): 1168-1175. DOI: 10.1038/ng.2757. [39] LIU ZL, MA JL, DONG SJ, et al. Study on the pathogenesis and prevention of novel coronavirus pneumonia based on Th17/Treg immune imbalance[J]. Chin J Pathophysiol, 2020, 36(10): 1913-1920. DOI: 10.3969/j.issn.1000-4718.2020.10.027.刘智霖, 马建岭, 董尚娟, 等. 基于Th17/Treg免疫失衡探讨新型冠状病毒肺炎的发病及防治[J]. 中国病理生理杂志, 2020, 36(10): 1913-1920. DOI: 10.3969/j.issn.1000-4718.2020.10.027. [40] LU D, SONG JH, MA ZJ, et al. Mechanism of Th17/Treg imbalance in patients with Echinococcus granulosus based on miRNA expression profile[J]. Chin J Schisto Control, 2022, 34(3): 277-285. DOI: 10.16250 / j. 32.1374.2022052.鲁迪, 宋佳卉, 马子建, 等. 基于miRNA表达谱解析细粒棘球蚴病患者体内Th17/Treg失衡机制[J]. 中国血吸虫病防治杂志, 2022, 34(3): 277-285. DOI: 10.16250/j.32.1374.2022052. [41] WANG H, NILOPAL TURXUN, ZHAO F, et al. Study on the relationship between JAK-STAT signaling pathway and Th17/Treg cell immune imbalance in myelodysplastic syndrome[J]. Mod Oncol, 2022, 30(10): 1826-1831. DOI: 10.3969/j.issn.1672-4992.2022.10.022.王欢, 尼罗帕尔·吐尔逊, 赵芳, 等. JAK-STAT信号通路与骨髓增生异常综合征Th17/Treg细胞免疫失调相关性的研究[J]. 现代肿瘤医学, 2022, 30(10): 1826-1831. DOI: 10.3969/j.issn.1672-4992.2022.10.022. [42] TUXUN T, WANG JH, LIN RY, et al. Th17/Treg imbalance in patients with liver cystic echinococcosis[J]. Parasite Immunol, 2012, 34(11): 520-527. DOI: 10.1111/j.1365-3024.2012.01383.x. [43] XUE XY, WU LP, ZHANG GQ, et al. Effects of quercitrin on PI3K-AKT signaling pathway and neurotrophic effect in rats in vitro[J]. Anti-infect Med, 2020, 17(9): 1252-1255. DOI: 10.13493 / j.i SSN 1672.7878.2020.09-004.薛小燕, 巫莉萍, 张桂青, 等. 槲皮苷对体外大鼠PI3K-AKT信号通路与神经营养作用影响的相关性研究[J]. 抗感染药学, 2020, 17(9): 1252-1255. DOI: 10.13493/j.issn.1672.7878.2020.09-004. [44] MICHALEK RD, GERRIETS VA, JACOBS SR, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets[J]. J Immunol, 2011, 186(6): 3299-3303. DOI: 10.4049/jimmunol.1003613. [45] LI Y. Research progress on the effect of glycosylation modification of PD-1/PD-L1 on tumor immunotherapy[J]. Fudan Univ J Med Sci, 2021, 48(5): 666-670. DOI: 10.3969/j.issn.1672-8467.2021.05.015.李胤. PD-1/PD-L1的糖基化修饰对肿瘤免疫治疗影响的研究进展[J]. 复旦学报(医学版), 2021, 48(5): 666-670. DOI: 10.3969/j.issn.1672-8467.2021.05.015. [46] WANG J, WANG WT. Progress of diagnosis and treatments for hepatic alveolar echinococcosis[J/CD]. Chin J Hepat Surg(Electronic Edition), 2022, 11(4): 351-355. DOI: 10.3877/cma.j.issn.2095-3232.2022.04.006.王健, 王文涛. 肝包虫病诊疗进展[J/CD]. 中华肝脏外科手术学电子杂志, 2022, 11(4): 351-355. DOI: 10.3877/cma.j.issn.2095-3232.2022.04.006. [47] ZHANG HT, LI X, TAO KS. Diagnosis and treatment specification for immunosuppressive therapy and rejection of liver transplantation in China (2019 edition)[J]. Ogran Transplant, 2021, 12(1): 8-14, 28. DOI: 10.3969/j.issn.1674-7445.2021.01.002.张洪涛, 李霄, 陶开山. 中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)[J]. 器官移植, 2021, 12(1): 8-14, 28. DOI: 10.3969/j.issn.1674-7445.2021.01.002. [48] ZHAO SY, ZHU HH, WANG XQ, et al. Hepatic multilocular spines ball status and progress of comprehensive treatment of larva disease[J]. Chin J Schisto Control, 2019, 31(6): 676-678. DOI: 10.16250 / j. 32.1374.2018086.赵顺云, 朱海宏, 王向前, 等. 肝多房棘球蚴病的综合治疗现状和进展[J]. 中国血吸虫病防治杂志, 2019, 31(6): 676-678. DOI: 10.16250/j.32.1374.2018086. [49] GUO YM, ZHU WJ, ZHAO SY, et al. Complexity of liver spines ball larva disease surgical treatment strategy research progress[J]. Chin J Schisto Control, 2018, 30(6): 705-708. DOI: 10.16250 / j. 32.1374.2018169.郭亚民, 朱文君, 赵顺云, 等. 复杂性肝棘球蚴病外科治疗策略研究进展[J]. 中国血吸虫病防治杂志, 2018, 30(6): 705-708. DOI: 10.16250/J.32.1374.2018169. -
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