Modern cancer immunotherapies are very effective, but they often have severe side effects that can lead to the discontinuation of treatment. Researchers at the University Medical Center Freiburg have now shown that a special light therapy for blood cells can significantly reduce these side effects without impairing tumour defence. Extracorporeal photopheresis (ECP) is the name given to the specific process that alleviates the inflammation caused by immunotherapy. They have 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 on 10 February 2025 in the journal Cancer Cell. This work is the result of 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 defence 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 Tumour Immunology and Immune Regulation at the Department of Internal Medicine I at the University Medical Center Freiburg, spokesperson for the Collaborative Research Centre 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 University Medical Center Freiburg.

Successful clinical trial

In a clinical study with 14 patients affected by severe inflammatory side effects, ECP showed great success. 92 per cent 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 specialised method

To date, extracorporeal photopheresis has mainly been used in very specialised cases in transplant medicine, for example in the treatment of graft-versus-host reactions following 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 tumour defence,’ 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 realisation 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."

Original Publication: 

Lukas M. Braun, Sophie Giesler, Geoffroy Andrieux, Roxane Riemer, Nana Talvard-Balland, Sandra Duquesne, Tamina Rückert, Susanne Unger, Stefanie Kreutmair, Melissa Zwick, Marie Follo, Alina Hartmann, Natascha Osswald, Wolfgang Melchinger, Stefanie Chapman, James A. Hutchinson, Sebastian Haferkamp, Leopold Torster, Julian Kött, Christoffer Gebhardt, Dirk Hellwig, Nikolaos Karantzelis, Till Wallrabenstein, Theresa Lowinus, Mehtap Yücel, Niklas Brehm, Justyna Rawluk, Dietmar Pfeifer, Peter Bronsert, Manuel Rogg, Sven Mattern, Mathias Heikenwälder, Stefano Fusco, Nisar P. Malek, Stephan Singer, Annette Schmitt-Graeff, Fatih Ceteci, Florian R. Greten, Bruce R. Blazar, Melanie Boerries, Natalie Köhler, Justus Duyster, Gabriele Ihorst, Silke Lassmann, Philip Keye, Susana Minguet, Dirk Schadendorf, Selma Ugurel, David Rafei-Shamsabadi, Robert Thimme, Peter Hasselblatt, Bertram Bengsch, Christoph Schell, Erika L. Pearce, Frank Meiss, Burkhard Becher, Carolin Funke-Lorenz, Jan-Malte Placke, Petya Apostolova, Robert Zeiser (2025) Adiponectin reduces immune checkpoint inhibitor-induced inflammation without blocking anti-tumor immunity. In: Cancer Cell. DOI: 10.1016/j.ccell.2025.01.004

CIBSS profile of Prof. Dr. Robert Zeiser

Original press release