Advancing immunosuppression in liver transplantation: A narrative review
Samuele Iesari a , # , Francesca Laura Nava a , # , Ilaria Elena Zais a , Laurent Coubeau b , c , Mariano Ferraresso a , d , Evaldo Favi a , d , ∗, Jan Lerut b
a General Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 15 Via della Commenda, 20122 Milan, Italy
b Institut de Recherche Expérimentale et Clinique, Universitécatholique de Louvain, 10 Avenue Hippocrate, 1200 Brussels, Belgium
c Service de Chirurgie et Transplantation Abdominale, Cliniques Universitaires Saint-Luc, 55 Avenue Hippocrate, 1200 Brussels, Belgium
d Department of Clinical Sciences and Community Health, Universitàdegli Studi di Milano, 19 Via della Commenda, 20122 Milan, Italy
∗Corresponding author at: General Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 15 Via della Commenda, 20122 Milan, Italy.
E-mail address: evaldo.favi@unimi.it (E. Favi).
# Contributed equally.
Abstract：Immunosuppression is essential to ensure recipient and graft survivals after liver transplantation (LT). However, our understanding and management of the immune system remain suboptimal. Current immunosuppressive therapy cannot selectively inhibit the graft-specific immune response and entails a significant risk of serious side effects, i.e., among others, de novo cancers, infections, cardiovascular events, renal failure, metabolic syndrome, and late graft fibrosis, with progressive loss of graft function. Pharmacological research, aimed to develop alternative immunosuppressive agents in LT, is behind other solid- organ transplantation subspecialties, and, therefore, the development of new compounds and strategies should get priority in LT. The research trajectories cover mechanisms to induce T-cell exhaustion, to in- hibit co-stimulation, to mitigate non-antigen-specific inflammatory response, and, lastly, to minimize the development and action of donor-specific antibodies. Moreover, while cellular modulation techniques are complex, active research is underway to foster the action of T-regulatory cells, to induce tolerogenic den- dritic cells, and to promote the function of B-regulatory cells. We herein discuss current lines of research in clinical immunosuppression, particularly focusing on possible applications in the LT setting.
2024, Vol. 23 
