UPMC and University of Pittsburgh clinician-scientists announced on Apr. 17 that they have successfully weaned several liver transplant patients off all immunosuppressant drugs for more than three years, following a first-in-human clinical trial using a unique "immune priming" therapy.
The findings are important because lifelong use of immunosuppressive drugs is standard after organ transplantation to prevent rejection, but these medications can cause serious side effects such as kidney damage, metabolic issues, infections, certain cancers, and diabetes. The study suggests there may be a way to reduce or eliminate the need for these drugs in some patients.
According to results published in Nature Communications, the trial involved infusing living donor liver transplant recipients with immune cells derived from their donors one week before surgery. A year after transplantation, eligible patients began tapering off immunosuppression under close monitoring. Senior author Angus Thomson said: "Long-term use of immunosuppressive drugs can harm the kidneys, causes metabolic complications, makes patients more susceptible to infections and certain types of cancer, as well as diabetes." UPMC performed 89 living donor liver transplants in 2025.
The process involved filtering white blood cells called monocytes from donors weeks before surgery and inducing them to become regulatory dendritic cells (DCregs). These DCregs were then given to recipients with the goal of teaching their immune systems to accept the new organ as friendly rather than foreign. Out of thirteen participants followed in this phase I/IIa trial started in 2017 with funding from UPMC Enterprises, eight were eligible for withdrawal attempts; four achieved complete withdrawal from immunosuppression without rejecting their transplanted livers. Three remained off medication for over three years.
This outcome represents a tolerance rate of about 37.5% among those eligible for early withdrawal—compared with approximately 13% historically among non-trial adult recipients deemed suitable for similar attempts—but researchers caution that larger studies are needed before drawing firm conclusions about efficacy.
First author Abhinav Humar said: "For as long as organ transplantation has been a field of medicine, tolerance has been its holy grail... And while we haven't hit a home run yet, we've definitely gotten on base by reliably and safely removing immunosuppression early after transplantation from a significant percentage of patients." The team plans further research including larger randomized trials and testing different protocols or cell sources. Thomson added: "There are so many tantalizing paths we could take to help our findings benefit many more patients... We are very interested in collaborating with other transplantation centers to accelerate and scale our clinical research."
