Liver and Bile

Nat Commun. 2026;17(1):3226

Humar A, Hadjiyannis Y, Macedo C, Tran LM, Elinoff BD, Hughes CB, Ganesh SR, Zahorchak AF, Ables EM, Styn MA, Landsittel D, Zeevi A, Lakkis FG, Metes DM, Thomson AW

Donor-derived regulatory dendritic cell infusion and early immunosuppressive drug withdrawal in living-donor liver transplantation: A phase I/IIa trial

Operational tolerance (OT) following complete immunosuppression withdrawal (ISW) is rare (~ 13%) in eligible adult liver transplant recipients when initiated 1–2-years post-transplant. Regulatory dendritic cells (DCregs) promote transplant tolerance in pre-clinical models and attenuate immune effector cells in humans. Here, we completed a first-in-human phase I/IIa trial (2-year recruitment; 5 ± 0.5 years follow-up) to evaluate the feasibility, safety and preliminary efficacy of pre-emptive donor-derived DCreg (ddDCreg) infusion 7-days pre-transplant in 15 prospective living-donor liver recipients. Two patients were excluded from analysis for reasons unrelated to the study. ISW began one year post-transplant in candidates with a quiescent/permissive protocol biopsy. ddDCreg infusions were safe, reproducible, and well-tolerated. One-year post-transplant, 8/13 patients were eligible for ISW, 4 achieved complete ISW, 3 remained off all immunosuppression for > 1 year. These 3 remained drug-free for 3.0 ± 0.17-years, reflecting a 37.5% OT rate in ISW-eligible recipients. Given the exploratory nature of this trial, additional studies to evaluate efficacy are needed.

DOI:  10.1038/s41467-026-71280-8