“Blood washing” with light makes cancer immunotherapies much more tolerable

Modern cancer immunotherapies are very effective, but often have severe side effects that can lead to discontinuation of therapy. Researchers at the University Medical Center Freiburg, including those from the German Cancer Consortium (DKTK), partner site Freiburg, have now shown that a special light therapy for blood cells can significantly reduce these side effects without impairing the tumor's immune response.

The so-called extracorporeal photopheresis (ECP) specifically alleviates the inflammation caused by immunotherapy. The researchers also discovered the mechanism behind it. 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

To date, extracorporeal photopheresis has 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 fat 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 knowledge about 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.”

Original publication: Braun, L.M., Giesler, S., Andrieux, G. et al. Adiponectin reduces immune checkpoint inhibitor-induced inflammation without blocking anti-tumor immunity. Cancer Cell, Volume 43, Issue 2, 269 - 291.e19.