留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

PD-1/PD-L1信号通路在肝移植免疫应答中的作用

陆晶 徐军明

陆晶, 徐军明. PD-1/PD-L1信号通路在肝移植免疫应答中的作用[J]. 器官移植, 2021, 12(4): 472-476. doi: 10.3969/j.issn.1674-7445.2021.04.015
引用本文: 陆晶, 徐军明. PD-1/PD-L1信号通路在肝移植免疫应答中的作用[J]. 器官移植, 2021, 12(4): 472-476. doi: 10.3969/j.issn.1674-7445.2021.04.015
Lu Jing, Xu Junming. Role of PD-1/PD-L1 signaling pathway in immune response of liver transplantation[J]. ORGAN TRANSPLANTATION, 2021, 12(4): 472-476. doi: 10.3969/j.issn.1674-7445.2021.04.015
Citation: Lu Jing, Xu Junming. Role of PD-1/PD-L1 signaling pathway in immune response of liver transplantation[J]. ORGAN TRANSPLANTATION, 2021, 12(4): 472-476. doi: 10.3969/j.issn.1674-7445.2021.04.015

PD-1/PD-L1信号通路在肝移植免疫应答中的作用

doi: 10.3969/j.issn.1674-7445.2021.04.015
基金项目: 

国家自然科学基金面上项目 81970568

国家自然科学基金面上项目 81670595

详细信息
    作者简介:

    陆晶,男,1997年生,硕士研究生,研究方向为肝移植,Email:lujing100@163.com

    通讯作者:

    徐军明,男,1971年生,博士,主任医师,研究方向为肝移植,Email:xjmsh@hotmail.com

  • 中图分类号: R617, R735.7

Role of PD-1/PD-L1 signaling pathway in immune response of liver transplantation

More Information
  • 摘要: 原发性肝癌(肝癌)是肝移植主要适应证之一,但术后肝癌复发严重影响肝移植的长期疗效。程序性细胞死亡蛋白1(PD-1)是一种免疫抑制分子,PD-1/程序性细胞死亡蛋白配体1(PD-L1)信号通路的激活在移植物免疫耐受中发挥重要作用。近年来,以PD-1/PD-L1抑制剂为代表的免疫检查点抑制剂已成为治疗晚期肝癌病人的有效手段之一,但能否用于肝移植受者仍存在较大的争议,其有效性和安全性仍有待研究。本文对PD-1/PD-L1在移植肝组织的表达、PD-1/PD-L1诱导移植免疫耐受的机制以及PD-1/PD-L1抑制剂在肝癌肝移植中的临床应用做一综述。

     

  • [1] 陆才德, 房炯泽. 肝癌肝移植研究进展[J]. 浙江医学, 2020, 42(14): 1459-1463. DOI: 10.12056/j.issn.1006-2785.2020.42.14.2019-1181.

    LU CD, FANG JZ. Advances in liver transplantation for liver cancer[J]. Zhejiang Med J, 2020, 42(14): 1459-1463. DOI: 10.12056/j.issn.1006-2785.2020.42.14.2019-1181.
    [2] 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.
    [3] DAI S, JIA R, ZHANG X, et al. The PD-1/PD-Ls pathway and autoimmune diseases[J]. Cell Immunol, 2014, 290(1): 72-79. DOI: 10.1016/j.cellimm.2014.05.006.
    [4] 潘思宇, 王志鑫, 周瀛, 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.

    PAN SY, WANG ZX, ZHOU Y, et al. Function and mechanism of action of the PD-1/PD-L1 pathway in liver diseases[J]. J Clin Hepatol, 2019, 35(3): 672-676. DOI: 10.3969/j.issn.1001-5256.2019.03.050.
    [5] UEKI S, CASTELLANETA A, YOSHIDA O, et al. Hepatic B7 homolog 1 expression is essential for controlling cold ischemia/reperfusion injury after mouse liver transplantation[J]. Hepatology, 2011, 54(1): 216-228. DOI: 10.1002/hep.24360.
    [6] MORITA M, FUJINO M, JIANG G, et al. PD-1/B7-H1 interaction contribute to the spontaneous acceptance of mouse liver allograft[J]. Am J Transplant, 2010, 10(1): 40-46. DOI: 10.1111/j.1600-6143.2009.02859.x.
    [7] LIU Z, YU X, REN W, et al. CD152 and PD-1 down-regulation on CD8 T cells is associated with human acute liver allograft rejection[J]. Transplant Proc, 2014, 46(10): 3511-3514. DOI: 10.1016/j.transproceed.2014.06.079.
    [8] SHI XL, MANCHAM S, HANSEN BE, et al. Counter-regulation of rejection activity against human liver grafts by donor PD-L1 and recipient PD-1 interaction[J]. J Hepatol, 2016, 64(6): 1274-1282. DOI: 10.1016/j.jhep.2016.02.034.
    [9] AYALA-MAR S, DONOSO-QUEZADA J, GONZÁLEZ-VALDEZ J. Clinical implications of exosomal PD-L1 in cancer immunotherapy[J]. J Immunol Res, 2021: 8839978. DOI: 10.1155/2021/8839978.
    [10] LIU Y, LIU S, WU C, et al. PD-1-mediated PI3K/Akt/mTOR, Caspase 9/Caspase 3 and ERK pathways are involved in regulating the apoptosis and proliferation of CD4+ and CD8+ T cells during BVDV infection in vitro[J]. Front Immunol, 2020, 11: 467. DOI: 10.3389/fimmu.2020.00467.
    [11] CHAUDHRI A, XIAO Y, KLEE AN, et al. PD-L1 binds to B7-1 only in cis on the same cell surface[J]. Cancer Immunol Res, 2018, 6(8): 921-929. DOI: 10.1158/2326-6066.CIR-17-0316.
    [12] DENG R, CASSADY K, LI X, et al. B7H1/CD80 interaction augments PD-1-dependent T cell apoptosis and ameliorates graft-versus-host disease[J]. J Immunol, 2015, 194(2): 560-574. DOI: 10.4049/jimmunol.1402157.
    [13] STATHOPOULOU C, GANGAPLARA A, MALLETT G, et al. PD-1 inhibitory receptor downregulates asparaginyl endopeptidase and maintains Foxp3 transcription factor stability in induced regulatory T cells[J]. Immunity, 2018, 49(2): 247-263. DOI: 10.1016/j.immuni.2018.05.006.
    [14] CAI J, WANG D, ZHANG G, et al. The role of PD-1/PD-L1 axis in treg development and function: implications for cancer immunotherapy[J]. Onco Targets Ther, 2019, 12: 8437-8445. DOI: 10.2147/OTT.S221340.
    [15] LEUNG CS, YANG KY, LI X, et al. Single-cell transcriptomics reveal that PD-1 mediates immune tolerance by regulating proliferation of regulatory T cells[J]. Genome Med, 2018, 10(1): 71. DOI: 10.1186/s13073-018-0581-y.
    [16] ONO Y, PEREZ-GUTIERREZ A, NAKAO T, et al. Graft-infiltrating PD-L1hi cross-dressed dendritic cells regulate antidonor T cell responses in mouse liver transplant tolerance[J]. Hepatology, 2018, 67(4): 1499-1515. DOI: 10.1002/hep.29529.
    [17] DE TONI EN, GERBES AL. Tapering of immunosuppression and sustained treatment with nivolumab in a liver transplant recipient[J]. Gastroenterology, 2017, 152(6): 1631-1633. DOI: 10.1053/j.gastro.2017.01.063.
    [18] GASSMANN D, WEILER S, MERTENS JC, et al. Liver allograft failure after nivolumab treatment-a case report with systematic literature research[J]. Transplant Direct, 2018, 4(8): e376. DOI: 10.1097/TXD.0000000000000814.
    [19] QIU J, TANG W, DU C. Immune checkpoint inhibitors in patients with recurrent hepatocellular carcinoma after liver transplantation: a case report and literature review[J]. Curr Cancer Drug Targets, 2020, 20(9): 720-727. DOI: 10.2174/1568009620666200520084415.
    [20] VARKARIS A, LEWIS DW, NUGENT FW. Preserved liver transplant after PD-1 pathway inhibitor for hepatocellular carcinoma[J]. Am J Gastroenterol, 2017, 112(12): 1895-1896. DOI: 10.1038/ajg.2017.387.
    [21] NORDNESS MF, HAMEL S, GODFREY CM, et al. Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: are checkpoint inhibitors safe for the pretransplant patient?[J]. Am J Transplant, 2020, 20(3): 879-883. DOI: 10.1111/ajt.15617.
    [22] TABRIZIAN P, FLORMAN SS, SCHWARTZ ME. PD-1 inhibitor as bridge therapy to liver transplantation?[J]. Am J Transplant, 2020, 21(5): 1979-1980. DOI: 10.1111/ajt.16448.
    [23] 崔春晓, 杨柳晓, 王颖, 等. 肝癌患者肝移植术前使用PD-1抑制剂对移植后排斥反应的影响[J]. 中国临床医学, 2020, 27(3): 444-447. DOI: 10.12025/j.issn.1008-6358.2020.20201005.

    CUI CX, YANG LX, WANG Y, et al. The effect of PD-1 inhibitor treatment before liver transplantation on posttransplant rejection in liver cancer patients[J]. Chin J Clin Med, 2020, 27(3): 444-447. DOI: 10.12025/j.issn.1008-6358.2020.20201005.
    [24] MUNKER S, DE TONI EN. Use of checkpoint inhibitors in liver transplant recipients[J]. United European Gastroenterol J, 2018, 6(7): 970-973. DOI: 10.1177/2050640618774631.
    [25] DE BRUYN P, VAN GESTEL D, OST P, et al. Immune checkpoint blockade for organ transplant patients with advanced cancer: how far can we go?[J]. Curr Opin Oncol, 2019, 31(2): 54-64. DOI: 10.1097/CCO.0000000000000505.
    [26] CHAE YK, GALVEZ C, ANKER JF, et al. Cancer immunotherapy in a neglected population: the current use and future of T-cell-mediated checkpoint inhibitors in organ transplant patients[J]. Cancer Treat Rev, 2018, 63: 116-121. DOI: 10.1016/j.ctrv.2017.12.004.
    [27] FISHER J, ZEITOUNI N, FAN W, et al. Immune checkpoint inhibitor therapy in solid organ transplant recipients: a patient-centered systematic review[J]. J Am Acad Dermatol, 2020, 82(6): 1490-1500. DOI: 10.1016/j.jaad.2019.07.005.
    [28] HU B, YANG XB, SANG XT. Liver graft rejection following immune checkpoint inhibitors treatment: a review[J]. Med Oncol, 2019, 36(11): 94. DOI: 10.1007/s12032-019-1316-7.
  • 加载中
图(1)
计量
  • 文章访问数:  161
  • HTML全文浏览量:  50
  • PDF下载量:  29
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-04-01
  • 网络出版日期:  2021-07-13
  • 刊出日期:  2021-07-15

目录

    /

    返回文章
    返回