Advancing immunosuppression in liver transplantation:A narrative reviewOA

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 im-munosuppressive therapy cannot selectively inhibit the graft-specific immune response and entails a sig-nificant 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.Pharma-cological 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.