TY - JOUR
T1 - Advances in Liver Transplantation
T2 - where are we in the pursuit of transplantation tolerance?
AU - Safinia, Niloufar
AU - Vaikunthanathan, Trishan
AU - Lechler, Robert Ian
AU - Sanchez-Fueyo, Alberto
AU - Lombardi, Giovanna
N1 - Funding Information:
We acknowledge Research Councils United Kingdom (RCUK) for the support. This research was funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London and/or the NIHR Clinical Research Facility. NS was funded by the Wellcome Trust Clinical Research Career Development Fellowship.
Funding Information:
We acknowledge Research Councils United Kingdom (RCUK) for the support. This research was?funded/supported by the National Institute for Health Research (NIHR)?Biomedical Research Centre based at?Guy's and St Thomas' NHS Foundation Trust and King's College London and/or the NIHR Clinical Research Facility. NS was funded by the Wellcome Trust Clinical Research Career Development Fellowship.
Publisher Copyright:
© 2021 Wiley-VCH GmbH
PY - 2021/10
Y1 - 2021/10
N2 - Liver transplantation is the ultimate treatment option for end-stage liver disease. Breakthroughs in surgical practice and immunosuppression have seen considerable advancements in survival after transplantation. However, the intricate management of immunosuppressive regimens, balancing desired immunological quiescence while minimizing toxicity has proven challenging. Diminishing improvements in long-term morbidity and mortality have been inextricably linked with the protracted use of these medications. As such, there is now enormous interest to devise protocols that will allow us to minimize or completely withdraw immunosuppressants after transplantation. Immunosuppression withdrawal trials have proved the reality of tolerance following liver transplantation, however, without intervention will only occur after several years at the risk of potential cumulative immunosuppression-related morbidity. Focus has now been directed at accelerating this phenomenon through tolerance-inducing strategies. In this regard, efforts have seen the use of regulatory cell immunotherapy. Here we focus particularly on regulatory T cells, discussing preclinical data that propagated several clinical trials of adoptive cell therapy in liver transplantation. Furthermore, we describe efforts to further optimize the specificity and survival of regulatory cell therapy guided by concurrent immunomonitoring studies and the development of novel technologies including chimeric antigen receptors and co-administration of low-dose IL-2.
AB - Liver transplantation is the ultimate treatment option for end-stage liver disease. Breakthroughs in surgical practice and immunosuppression have seen considerable advancements in survival after transplantation. However, the intricate management of immunosuppressive regimens, balancing desired immunological quiescence while minimizing toxicity has proven challenging. Diminishing improvements in long-term morbidity and mortality have been inextricably linked with the protracted use of these medications. As such, there is now enormous interest to devise protocols that will allow us to minimize or completely withdraw immunosuppressants after transplantation. Immunosuppression withdrawal trials have proved the reality of tolerance following liver transplantation, however, without intervention will only occur after several years at the risk of potential cumulative immunosuppression-related morbidity. Focus has now been directed at accelerating this phenomenon through tolerance-inducing strategies. In this regard, efforts have seen the use of regulatory cell immunotherapy. Here we focus particularly on regulatory T cells, discussing preclinical data that propagated several clinical trials of adoptive cell therapy in liver transplantation. Furthermore, we describe efforts to further optimize the specificity and survival of regulatory cell therapy guided by concurrent immunomonitoring studies and the development of novel technologies including chimeric antigen receptors and co-administration of low-dose IL-2.
KW - immunosuppression withdrawal
KW - immunotherapy
KW - liver transplantation
KW - regulatory T cells
KW - tolerance
UR - http://www.scopus.com/inward/record.url?scp=85114150226&partnerID=8YFLogxK
U2 - 10.1002/eji.202048875
DO - 10.1002/eji.202048875
M3 - Article
C2 - 34375446
AN - SCOPUS:85114150226
SN - 0014-2980
VL - 51
SP - 2373
EP - 2386
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 10
ER -