Induction of Clinical Operational Tolerance Through Immunosuppression Minimization: Less Is More?

The goal of achieving clinical operational tolerance in liver transplantation has sparked significant interest, driven by the desire to mitigate the long-term adverse effects of immunosuppression. Advances in understanding the immunological mechanisms underpinning operational tolerance in liver transplantation have highlighted the central role of regulatory T cells and tolerogenic dendritic cells. These cells actively suppress effector immune responses and aid in achieving operational tolerance. Immunosuppressive medication differentially influences the expansion, survival, and function of these cells, demonstrating the importance of understanding the potential of immunosuppressive regimens to optimize the possibility of achieving an immunosuppression-free state. The potential of stepwise immunosuppressive reduction to achieve operational tolerance without compromising graft function has been demonstrated. The immunosuppressive withdrawal protocols underline the feasibility and safety of immunosuppressive withdrawal in selected liver transplant recipients, highlighting factors such as time since transplantation, recipient age, and gender as strong predictors of success. Furthermore, minimization of immunosuppressive, even early post transplantation, has been shown to be successful and sets the stage for successful immunosuppression withdrawal later. This review highlights the necessity to optimize immunosuppressive regimens by demonstrating its possibility to aid in achieving minimal immunosuppressive to maximize success rates of drug withdrawal and diminish the cumulative immunosuppressive related complications to increase the quality of life of liver transplant recipients.