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• Posted October 16, 2023

Donor's Immune Cells Could Help Transplant Recipients Avoid Organ Rejection

A liver transplant can give people a new lease on life, but at the cost of lifelong immune-suppressing medication and its risks. Now an innovative approach to reduce, or possibly eliminate, certain patients' reliance on those drugs is showing early promise.

The tactic is aimed at priming a transplant recipient's immune system to better tolerate liver tissue from a living donor. A week before the transplant, the recipient receives an infusion of specific immune system cells from the donor -- ones that, in theory, could tone down any immune system attack on the new "foreign" liver.

In an early study of 13 patients who received liver tissue from a living donor, researchers found that the approach was safe and feasible.

And one year later, the patients were showing signs of a modified immune response to the donor liver, said senior researcher Angus Thomson, a professor of immunology and surgery at the University of Pittsburgh School of Medicine.

That suggests, Thomson said, that it might be possible to taper patients' doses of immune-suppressing medication, or wean them off of it.

The findings, published Oct. 11 in the journal Science Translational Medicine, are "encouraging," according to an expert not involved in the research.

"Any strategy that decreases the amount of immunosuppression needed for transplant patients is important," said Dr. Chris Sonnenday, surgical director of the living-donor liver transplantation program at the University of Michigan.

That chronic immune suppression, Sonnenday said, is responsible for most of the long-term health risks that transplant recipients face -- including not only infections, but various types of cancer, and kidney and heart disease.

Sonnenday said that at this point, it's unclear whether the immune cell infusion will ultimately allow patients to stop their anti-rejection drugs.

"The immune system is complex and may be stimulated by other events besides just the transplanted organ," said Sonnenday, who is also a member of the American Liver Foundation's transplant work group.

Still, he said, any strategy that could at least reduce patients' need for immune suppression would likely have benefits.

In the United States, most liver transplants come from deceased donors, according to the ALF. But some involve a living donor, often a relative or friend of the recipient.

That's possible because the liver is unique among human organs in that it can regenerate. Donors give a portion of their liver to the recipient, and the tissue regrows to full size in both.

In the new study, Thomson and his colleagues wanted to see if, ahead of such a transplant, they could set up a friendlier immune system environment for the donor liver.

A few weeks ahead of a patient's planned transplant, the donor gave a blood sample, from which the researchers isolated monocytes, a type of white blood cell. Then in the lab, they coaxed those monocytes to form regulatory dendritic cells, or DCregs -- which are key "orchestrators" of the immune response, Thomson said.

Each transplant recipient received an infusion of their donor's DCregs one week before the transplant surgery. Everything after that was business as usual -- including the use of standard immune-suppressing medication after the transplant.

First and foremost, Thomson said, the tactic had to prove safe. In theory, the DCreg infusion could have caused a "non-specific" dampening of recipients' immune responses, for instance.

Fortunately, Thomson said, there was no evidence of that in the 13 patients his team followed for a year. They fared similarly to a comparison group of 40 patients who'd received liver tissue from living donors, but without DCreg infusions.

Beyond that, the researchers saw promising signals when they examined patients' immune system activity. Those who'd received DCregs had a reduction in certain other immune system cells that are associated with an increased risk of transplant rejection.

"I think the most reasonable interpretation of this innovative study is that there appeared to be a trend in the study group towards needing slightly less immunosuppressive medication, when compared to the control group," Sonnenday said.

But the ultimate test remains.

Thomson said that at the one-year mark, patients in the study were to have tests to see how their new liver was doing. From there, the transplant team would decide if it was safe to try reducing their immune-suppressing medication.

Those results will be reported in the future. If all goes well, Thomson said, larger studies, done at multiple medical centers, will be needed.

Interestingly, in this study, the infused DCregs lasted for only a few days in the study patients' bodies. But based on prior lab research, Thomson explained, that short stay might be enough.

The donor DCregs, he said, are able to release tiny particles called exosomes, which allow cells to communicate with one another. The researchers believe that those particles are "instructing" the recipient's own immune cells to tone down their response to the donor liver.

More information

The American Liver Foundation has more on liver transplantation.

SOURCES: Angus Thomson, PhD, DSc, professor, immunology and surgery, University of Pittsburgh School of Medicine, Pittsburgh; Chris Sonnenday, MD, MHS, director, Transplant Center, and surgical director, living donor liver transplantation, University of Michigan Health, Ann Arbor; Science Translational Medicine, Oct. 11, 2023, online