City of Hope researchers unveil thymus regeneration therapy for immune system repair

Scientists at City of Hope, one of the most renowned cancer research and treatment institutions in the United States, have uncovered a novel method to restore thymic function in patients undergoing cancer treatments. Their latest study, published in Immunity, reveals that a specific subset of regulatory T cells (Tregs) plays a crucial role in thymus regeneration therapy, offering a new avenue for immune system repair and cancer treatment recovery.

The research, led by Andri Lemarquis, M.D., Ph.D., a staff scientist at City of Hope, identifies a unique immune cell population that recirculates back into the thymus after damage, promoting tissue repair through the secretion of a growth factor called amphiregulin. The study, conducted in murine models and validated in human tissue samples, presents a promising therapeutic approach to reversing thymic atrophy, a common consequence of aging, stress, and cancer treatments.

Why Is the Thymus Gland Crucial for Immune System Repair?

The thymus gland, located between the lungs and above the heart, is an essential organ in immune function. It produces T cells, which serve as the body’s defense against infections, malignancies, and autoimmune diseases. However, this vital organ is highly vulnerable to deterioration caused by chemotherapy, radiation, infections, and aging.

“When the thymus gland shrinks, it significantly reduces the production of protective T cells, leaving patients susceptible to severe infections and immune dysfunction,” explained Dr. Lemarquis. “This loss of immune resilience is a major challenge in cancer treatment recovery, and our study demonstrates a potential solution through thymus regeneration therapy.”

How Does Thymus Regeneration Therapy Work?

The research team sought to understand the natural mechanisms behind thymic repair by studying murine models exposed to cancer therapies. Using advanced imaging and computational analysis, they identified a previously unrecognized population of Tregs that infiltrates the thymus gland after injury and releases amphiregulin, a growth factor critical for immune system repair.

Further experiments showed that injecting these Tregs into the bloodstream resulted in their migration back to the thymus, where they activated regenerative pathways. When the same process was tested on human thymic tissue samples, researchers observed identical results, confirming the potential for clinical applications in thymus regeneration therapy.

“We found that Tregs are not only essential for immune regulation but also play a previously unknown role in tissue regeneration,” noted Dr. Lemarquis. “This opens new possibilities for harnessing immune cells to aid in cancer treatment recovery and improve immune system repair in patients with compromised immunity.”

Can Thymus Regeneration Therapy Benefit Older Patients?

A surprising revelation from the study was that thymus regeneration therapy could also be effective in aging populations. It has long been believed that the thymus gland loses its ability to regenerate over time, making older individuals more susceptible to cancers, infections, and autoimmune disorders.

However, the research demonstrated that when Tregs were transferred into aged mice undergoing cancer therapies, their immune function improved, and thymic regeneration was successfully induced.

“These findings challenge the long-standing assumption that thymic degeneration in aging is irreversible,” said Dr. Lemarquis. “Our results indicate that thymus regeneration therapy could be a powerful tool for improving immune system repair in elderly patients receiving cancer treatments.”

What Are the Future Implications of Thymus Regeneration Therapy?

This breakthrough builds upon decades of research initiated by Marcel van den Brink, M.D., Ph.D., President of City of Hope Los Angeles and National Medical Center, who has pioneered studies on immune reconstitution in cancer treatment recovery. His extensive work provided the foundation for this new avenue of exploration.

The next phase of research involves analyzing a large database of human thymic samples to further identify molecular pathways that can enhance thymus regeneration therapy. Scientists are also investigating synthetic biology approaches to genetically engineer T cells that overproduce amphiregulin, potentially leading to a new class of regenerative immunotherapies.

“We have assembled a dedicated thymic research program at City of Hope, bringing together computational biologists, immunologists, and clinical researchers to translate these findings into real-world applications,” said Dr. Lemarquis. “We believe that Tregs and amphiregulin-based therapies hold great promise for cancer treatment recovery and immune system repair.”

Who Else Contributed to the Study?

The study, titled “Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following thymic damage,” was conducted in collaboration with researchers from Memorial Sloan Kettering Cancer Center, the University of Gothenburg, Bambino Gesù Children’s Hospital, New York-Presbyterian Morgan Stanley Children’s Hospital, the University of Washington, Fred Hutchinson Cancer Center, and Weill Cornell Medical College.

The research was funded by the National Cancer Institute, the National Heart, Lung, and Blood Institute, the National Institute on Aging, and DKMS.