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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 4
Apr.  2023
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Article Contents

Application of immune checkpoint inhibitors in liver transplantation for patients with hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2023.04.030
Research funding:

Gansu Provincial Key R&D Program (20YF8FA099);

Gansu Provincial Youth Science and Technology Fund (20JR10RA016);

Gansu Provincial Clinical Medical Research Centre for Non-infectious Liver Diseases (21JR7RA017);

Scientific Research Plan of Gansu Provincial Health Commission (GSWSKY2021-047)

More Information
  • Corresponding author: YU Xiaohui, yuxiaohui@126.com (ORCID: 0000-0002-8633-3281)
  • Received Date: 2022-07-31
  • Accepted Date: 2022-09-18
  • Published Date: 2023-04-20
  • Liver transplantation, as one of the radical treatment strategies for hepatocellular carcinoma, has a good clinical effect in patients meeting the Milan criteria; however, the high recurrence rate and metastasis rate after surgery bring great challenges to the long-term survival of such patients. Therefore, how to improve long-term survival rate and reduce postoperative tumor metastasis has become a key problem that needs to be solved urgently. In recent years, immune checkpoint inhibitors (ICIs), with their good safety and objective reactivity, have provided a new opportunity for the treatment of patients with advanced liver cancer and have become potential candidates for improving the therapeutic effect of liver transplantation. At present, early clinical studies have reported the unique advantages of ICIs used alone or in combination in downstaging or bridging therapy before liver transplantation for hepatocellular carcinoma and adjuvant therapy after liver transplantation. Therefore, this article reviews the clinical trials of ICIs in liver transplantation for hepatocellular carcinoma and the advances in the application of ICIs in recent years and discuss its safety and efficacy, in order to provide a certain reference for clinical medication.

     

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  • [1]
    SUNG H, FERLAY J, SIEGEL RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.
    [2]
    Committee of Liver Transplantation, Chinese College of Transplant Doctors, Chinese Medical Doctor Association; Section of Liver Transplantation, Chinese Society of Organ Transplantation, Chinese Medical Association. Chinese expert consensus on application of sirolimus in liver transplantation for hepatocellular carcinoma(2020 edition)[J]. J Clin Hepatol, 2020, 36(11): 2429-2434. DOI: 10.3969/j.issn.1001-5256.2020.11.007.

    中国医师协会器官移植医师分会肝移植学组, 中华医学会器官移植学分会肝移植学组. 西罗莫司在肝癌肝移植中应用的中国专家共识(2020版)[J]. 临床肝胆病杂志, 2020, 36(11): 2429-2434. DOI: 10.3969/j.issn.1001-5256.2020.11.007.
    [3]
    EL-KHOUEIRY AB, SANGRO B, YAU T, 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. DOI: 10.1016/S0140-6736(17)31046-2.
    [4]
    ZENG L, SU J, QIU W, et al. Survival outcomes and safety of programmed cell death/programmed cell death ligand 1 inhibitors for unresectable hepatocellular carcinoma: result from phase Ⅲ trials[J]. Cancer Control, 2022, 29: 10732748221092924. DOI: 10.1177/10732748221092924.
    [5]
    YAU T, KANG YK, KIM TY, et al. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: the checkmate 040 randomized clinical trial[J]. JAMA Oncol, 2020, 6(11): e204564. DOI: 10.1001/jamaoncol.2020.4564.
    [6]
    TSUNG I, WORDEN FP, FONTANA RJ. A pilot study of checkpoint inhibitors in solid organ transplant recipients with metastatic cutaneous squamous cell carcinoma[J]. Oncologist, 2021, 26(2): 133-138. DOI: 10.1002/onco.13539.
    [7]
    LEONETTI A, WEVER B, MAZZASCHI G, et al. Molecular basis and rationale for combining immune checkpoint inhibitors with chemotherapy in non-small cell lung cancer[J]. Drug Resist Updat, 2019, 46: 100644. DOI: 10.1016/j.drup.2019.100644.
    [8]
    MURAKAMI N, MULVANEY P, DANESH M, et al. A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant[J]. Kidney Int, 2021, 100(1): 196-205. DOI: 10.1016/j.kint.2020.12.015.
    [9]
    DOROSHOW DB, BHALLA S, BEASLEY MB, et al. PD-L1 as a biomarker of response to immune-checkpoint inhibitors[J]. Nat Rev Clin Oncol, 2021, 18(6): 345-362. DOI: 10.1038/s41571-021-00473-5.
    [10]
    SHARMA P, SIDDIQUI BA, ANANDHAN S, et al. The next decade of immune checkpoint therapy[J]. Cancer Discov, 2021, 11(4): 838-857. DOI: 10.1158/2159-8290.CD-20-1680.
    [11]
    LI X, WANG Y, YANG H, et al. Liver and hepatocyte transplantation: What can pigs contribute?[J]. Front Immunol, 2021, 12: 802692. DOI: 10.3389/fimmu.2021.802692.
    [12]
    HAN CZ, WEI Q, XU X. Transplant oncology creates a new era of liver transplantation for the treatment of liver cancer[J]. J Clin Hepatol, 2021, 37(2): 253-256. DOI: 10.3969/j.issn.1001-5256.2021.02.002.

    韩承祚, 卫强, 徐骁. 移植肿瘤学开创肝移植治疗肝癌新时代[J]. 临床肝胆病杂志, 2021, 37(2): 253-256. DOI: 10.3969/j.issn.1001-5256.2021.02.002.
    [13]
    JI R, DOU KF, XU H. Prevention and management of recurrence and metastasis of hepatocellular carcinoma after liver transplantation[J]. J Clin Hepatol, 2014, 30(1): 7-10. DOI: 10.3969/j.issn.1001-5256.2014.01.003.

    季茹, 窦科峰, 许辉. 肝细胞癌患者肝移植术后肿瘤复发转移的防治[J]. 临床肝胆病杂志, 2014, 30(1): 7-10. DOI: 10.3969/j.issn.1001-5256.2014.01.003.
    [14]
    JIANG C, JING S, ZHOU H, et al. Efficacy and prognostic factors of trans-arterial chemoembolization combined with stereotactic body radiation therapy for BCLC stage B hepatocellular carcinoma[J]. Front Oncol, 2021, 11: 640461. DOI: 10.3389/fonc.2021.640461.
    [15]
    KUDO M. A new treatment option for intermediate-stage hepatocellular carcinoma with high tumor burden: initial lenvatinib therapy with subsequent selective TACE[J]. Liver Cancer, 2019, 8(5): 299-311. DOI: 10.1159/000502905.
    [16]
    LAWAL G, XIAO Y, RAHNEMAI-AZAR AA, et al. The immunology of hepatocellular carcinoma[J]. Vaccines (Basel), 2021, 9(10): 1184. DOI: 10.3390/vaccines9101184.
    [17]
    SCHWACHA-EIPPER B, MINCIUNA I, BANZ V, et al. Immunotherapy as a downstaging therapy for liver transplantation[J]. Hepatology, 2020, 72(4): 1488-1490. DOI: 10.1002/hep.31234.
    [18]
    YE Q, LING S, ZHENG S, et al. Liquid biopsy in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA[J]. Mol Cancer, 2019, 18(1): 114. DOI: 10.1186/s12943-019-1043-x.
    [19]
    PELIZZARO F, GAMBATO M, GRINGERI E, et al Management of hepatocellular carcinoma recurrence after liver transplantation[J]. Cancers (Basel), 2021, 13(19): 4882. DOI: 10.3390/cancers13194882.
    [20]
    OWOYEMI I, VAUGHAN LE, COSTELLO CM, et al. Clinical outcomes of solid organ transplant recipients with metastatic cancers who are treated with immune checkpoint inhibitors: A single-center analysis[J]. Cancer, 2020, 126(21): 4780-4787. DOI: 10.1002/cncr.33134.
    [21]
    AMJAD W, KOTIAH S, GUPTA A, et al. Successful treatment of disseminated hepatocellular carcinoma after liver transplantation with nivolumab[J]. J Clin Exp Hepatol, 2020, 10(2): 185-187. DOI: 10.1016/j.jceh.2019.11.009.
    [22]
    ZHUANG L, MOU HB, YU LF, et al. Immune checkpoint inhibitor for hepatocellular carcinoma recurrence after liver transplantation[J]. Hepatobiliary Pancreat Dis Int, 2020, 19(1): 91-93. DOI: 10.1016/j.hbpd.2019.09.011.
    [23]
    FINN RS, RYOO BY, MERLE P, et al. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: A randomized, double-blind, phase iii trial[J]. J Clin Oncol, 2020, 38(3): 193-202. DOI: 10.1200/JCO.19.01307.
    [24]
    YAU T, PARK JW, FINN RS, et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial[J]. Lancet Oncol, 2022, 23(1): 77-90. DOI: 10.1016/S1470-2045(21)00604-5.
    [25]
    DELYON J, ZUBER J, DORENT R, et al. Immune checkpoint inhibitors in transplantation-a case series and comprehensive review of current knowledge[J]. Transplantation, 2021, 105(1): 67-78. DOI: 10.1097/TP.0000000000003292.
    [26]
    SHI GM, WANG J, HUANG XW, et al. Graft programmed death ligand 1 expression as a marker for transplant rejection following anti-programmed death 1 immunotherapy for recurrent liver tumors[J]. Liver Transpl, 2021, 27(3): 444-449. DOI: 10.1002/lt.25887.
    [27]
    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.
    [28]
    CHEN GH, WANG GB, HUANG F, et al. Pretransplant use of toripalimab for hepatocellular carcinoma resulting in fatal acute hepatic necrosis in the immediate postoperative period[J]. Transpl Immunol, 2021, 66: 101386. DOI: 10.1016/j.trim.2021.101386.
    [29]
    BRAHMER JR, DRAKE CG, WOLLNER I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates[J]. J Clin Oncol, 2010, 28(19): 3167-3175. DOI: 10.1200/JCO.2009.26.7609.
    [30]
    GAO Q, ANWAR IJ, ABRAHAM N, et al. Liver transplantation for hepatocellular carcinoma after downstaging or bridging therapy with immune checkpoint inhibitors[J]. Cancers (Basel), 2021, 13(24): 6307. DOI: 10.3390/cancers13246307.
    [31]
    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.
    [32]
    LIU ZB, WU JS, LIN DD, et al. Safety of PD-1 inhibitor in preoperative treatment of liver transplantation for liver cancer[J]. Ogran Transplant, 2021, 12(4): 445-449. DOI: 10.3969/j.issn.1674-7445.2021.04.011.

    刘召波, 武聚山, 林栋栋, 等. PD-1抑制剂用于肝癌肝移植术前治疗的安全性探讨[J]. 器官移植, 2021, 12(4): 445-449. DOI: 10.3969/j.issn.1674-7445.2021.04.011.
    [33]
    ClinicalTrials. gov. Combination camrelizumab (SHR-1210) and apatinib for downstaging/bridging of HCC before liver transplant[EB/OL]. (2019-07-29)[2022-07-28]. https://clinicaltrials.gov/ct2/show/NCT04035876.
    [34]
    ClinicalTrials. gov. Pembrolizumab and LENvatinib in participants with hepatocellular carcinoma (HCC) before liver transplant (PLENTY202001)[EB/OL]. (2020-06-11)[2022-07-28]. https://clinicaltrials.gov/ct2/show/NCT04425226.
    [35]
    ClinicalTrials. gov. Atezolizumab and bevacizumab pre-liver transplantation for patients with hepatocellular carcinoma beyond milan criteria[EB/OL]. (2022-01-11)[2022-07-28]. https://clinicaltrials.gov/ct2/show/NCT05185505.
    [36]
    ClinicalTrials. gov. Durvalumab (MEDI4736) and tremelimumab for hepatocellular carcinoma in patients listed for a liver transplant[EB/OL]. (2021-08-30)[2022-07-28]. https://clinicaltrials.gov/ct2/show/NCT05027425.
    [37]
    ClinicalTrials. gov. Durvalumab and lenvatinib in participants with locally advanced and metastatic hepatocellular carcinoma (Dulect2020-1) (Dulect2020-1)[EB/OL]. (2020-06-23)[2022-07-28]. https://clinicaltrials.gov/ct2/show/NCT04443322.
    [38]
    ClinicalTrials. gov. Safety and efficacy of camrelizumab (Anti-PD-1 Antibody) in recurrent HCC after liver transplantation[EB/OL]. (2020-09-25)[2022-07-28]. https://clinicaltrials.gov/ct2/show/NCT04564313.
    [39]
    ClinicalTrials. gov. IMRT plus PD-1 blockade and lenvatinib for HCC with PVTT (Vp3) before liver transplantation (iPLENTY-pvtt)[EB/OL]. (2022-04-21)[2022-07-28]. https://clinicaltrials.gov/ct2/show/NCT05339581.
    [40]
    ClinicalTrials. gov. Sequential PD-1/PD-L1 inhibitor and LENvatinib in TLCT and refractory hepatoblastoma after chemotherapy (sPLENTY-pc)[EB/OL]. (2022-04-11)[2022-07-28]. https://clinicaltrials.gov/ct2/show/NCT05322187.
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