Wir überwinden Grenzen

Blood cells irradiated with UV light lead to reduced inflammatory reaction / Fat metabolism molecule controls immune calming / Success in clinical study

"Blood washing" with light makes cancer immunotherapies much more tolerable

Blood cells irradiated with UV light lead to reduced inflammatory reaction / Fat metabolism molecule controls immune calming / Success in clinical study

Modern cancer immunotherapies are very effective, but often have severe side effects that can lead to discontinuation of treatment. Researchers at the Freiburg University Medical Center have now shown that a special light therapy for blood cells can significantly reduce these side effects without impairing tumor defense. Extracorporeal photopheresis (ECP) specifically alleviates the inflammation caused by immunotherapy. The researchers also discovered the mechanism behind this. They showed that the body's own molecule adiponectin, known from fat metabolism, regulates inflammation. The results were published in the journal Cancer Cell on February 10, 2025. The work is based on an intensive collaboration between many scientists from Freiburg, in particular the Departments of Internal Medicine I and II at the University Medical Center Freiburg, and researchers from Baltimore, USA.

"We were able to stop the side effects of cancer immunotherapy as far as possible. What is particularly exciting is that the body's defense against cancer does not suffer as a result. This significantly improves the quality of life of cancer patients," says Prof. Dr. Robert Zeiser, Head of the Department of Tumor Immunology and Immune Regulation at the Department of Internal Medicine I at the Freiburg University Medical Center, spokesperson of the Collaborative Research Center 1479 "OncoEscape" and member of the Cluster of Excellence CIBSS - Centre for Integrative Biological Signalling at the University of Freiburg. "In the future, many patients could benefit from immunotherapy for whom this has been too burdensome up to now," says Prof. Dr. Justus Duyster, Medical Director of the Department of Internal Medicine I at the Freiburg University Medical Center.

Successful clinical study
In a clinical study with 14 patients affected by severe inflammatory side effects, ECP showed great success. 92 percent of participants reported a significant improvement in their symptoms, and all patients with inflammatory bowel disease (colitis) were completely cured. In addition, the dosage of anti-inflammatory medication such as cortisone, which often has severe side effects, was reduced in all patients.

New application for a specialized method
Extracorporeal photopheresis has so far mainly been used in very specific cases in transplant medicine, for example in the treatment of graft-versus-host reactions after stem cell transplants. In this process, immune cells are removed from the patient, irradiated with UV light and returned to the body. These modified cells send out signals that calm the immune system.

Adiponectin: Unexpected player from the fat metabolism
Particularly surprising was the discovery that the effect of ECP is controlled by adiponectin - a molecule that was previously known primarily for its role in fat metabolism. "We were able to show that adiponectin specifically reduces pro-inflammatory cells in tissues such as the intestine without weakening the tumor defense," says Lukas Braun, first author and molecular physician in Zeiser's research group.

"It was unexpected that a molecule from the lipid metabolism could influence the immune system in such a targeted way," explains Prof. Zeiser. "This discovery could also open up new possibilities for the treatment of inflammatory diseases."

"New perspectives for targeted therapies"
"The ECP in combination with the discovery of the central role of adiponectin offers new perspectives for the targeted treatment of side effects of immunotherapies," says Zeiser. "Future studies should now confirm the results in larger patient groups and further investigate the potential of adiponectin."

Image 1: Prof. Dr. Robert Zeiser (left) and first author Lukas Braun discuss how a patient's intestinal tissue responded to the new therapy. 
Image source: Freiburg University Medical Center

Image 2: Intestinal tissue of a patient before (left) and after extracorporeal photopheresis (right). Various immune cells are marked in green, light blue, red, yellow, pink and pink. Significantly fewer inflammatory messengers are present after treatment. 
Image source: Freiburg University Medical Center

Original publication:
Adiponectin reduces immune checkpoint inhibitor-induced inflammation without blocking anti-tumor immunity. Cancer Cell, February 10, 2025.

DOI: 10.1016/j.ccell.2025.01.004

Link to the study: https://www.cell.com/cancer-cell/fulltext/S1535-6108(25)00022-4