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Immunotherapy in liver transplantation

  • Didier Samuel
    Affiliations
    AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France

    Univ Paris-Sud, UMR-S 1193, Université Paris-Saclay, Villejuif, F-94800, France

    Inserm, Unité 1193, Université Paris-Saclay, Villejuif, F-94800, France

    Hepatinov, Villejuif, F-94800, France
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  • Alberto Sanchez-Fueyo
    Correspondence
    Corresponding author. Address: Institute of Liver Studies, MRC Centre for Transplantation, King’s College Hospital, King’s College London, London, UK.
    Affiliations
    Institute of Liver Studies, MRC Centre for Transplantation, King’s College Hospital, King’s College London, London, UK
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Published:August 22, 2017DOI:https://doi.org/10.1016/j.jhep.2017.05.013
      Immunosuppressive regimens that contain calcineurin inhibitors effectively target recipient T cells, successfully prevent acute cellular rejection, and remain the mainstay immunosuppressant following liver transplantation. However, these regimens have many off target effects and are associated with significant toxicity. mTOR inhibitors provide some advantages over calcineurin inhibitors (e.g. anticancer properties, reduced nephrotoxicity), but have many other side effects, and are mainly used to reduce the overall calcineurin inhibitor exposure. Basiliximab (monoclonal antibody directed against the alpha chain of the IL-2 receptor) and other antibodies are given as induction therapy during the first hours following transplantation as a means to reduce or delay the administration of calcineurin inhibitors, and have also been used to treat steroid-resistant rejection. Azathioprine and mycophenolic acid are considered not potent enough to be used as monotherapy, and are typically administered in combination with calcineurin inhibitors in an attempt to reduce their nephrotoxicity.
      • Adams D.H.
      • Sanchez-Fueyo A.
      • Samuel D.
      From immunosuppression to tolerance.
      . Developments in the field of experimental immunology clearly demonstrate that it is possible to re-educate the immune system to accept foreign tissues in the absence of life-long immunosuppression by controlling effector immune responses, and at the same time promoting the function of graft-protecting immune regulatory cells. These findings are particularly relevant to human liver transplantation, given that liver allografts are less immunogenic than other organs, and, years after transplantation, are spontaneously accepted in a small group of patients.
      • Clavien P.A.
      • Muller X.
      • de Oliveira M.L.
      • Dutkowski P.
      • Sanchez-Fueyo A.
      Can immunosuppression be stopped after liver transplantation?.

      Abbreviations:

      Tregs (CD4+CD25+Foxp3+regulatory T cells), CD8 regs (CD8+ regulatory T cells), Bregs (regulatory B cell subsets), Tol-DC (tolerogenic dendritic cell subsets), MDSC (myeloid derived suppressor cells), NK/NKT (natural killer/natural killer T cells)
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