Braun, Lukas M. and Giesler, Sophie and Andrieux, Geoffroy and Riemer, Roxane and Talvard-Balland, Nana and Duquesne, Sandra and Rueckert, Tamina and Unger, Susanne and Kreutmair, Stefanie and Zwick, Melissa and Follo, Marie and Hartmann, Alina and Osswald, Natascha and Melchinger, Wolfgang and Chapman, Stefanie and Hutchinson, James A. and Haferkamp, Sebastian and Torster, Leopold and Koett, Julian and Gebhardt, Christoffer and Hellwig, Dirk and Karantzelis, Nikolaos and Wallrabenstein, Till and Lowinus, Theresa and Yuecel, Mehtap and Brehm, Niklas and Rawluk, Justyna and Pfeifer, Dietmar and Bronsert, Peter and Rogg, Manuel and Mattern, Sven and Heikenwaelder, Mathias and Fusco, Stefano and Malek, Nisar P. and Singer, Stephan and Schmitt-Graeff, Annette and Ceteci, Fatih and Greten, Florian R. and Blazar, Bruce R. and Boerries, Melanie and Koehler, Natalie and Duyster, Justus and Ihorst, Gabriele and Lassmann, Silke and Keye, Philip and Minguet, Susana and Schadendorf, Dirk and Ugurel, Selma and Rafei-Shamsabadi, David and Thimme, Robert and Hasselblatt, Peter and Bengsch, Bertram and Schell, Christoph and Pearce, Erika L. and Meiss, Frank and Becher, Burkhard and Funke-Lorenz, Carolin and Placke, Jan-Malte and Apostolova, Petya and Zeiser, Robert (2025) Adiponectin reduces immune checkpoint inhibitor-induced inflammation without blocking anti-tumor immunity. CANCER CELL, 43 (2). ISSN 1535-6108, 1878-3686
Full text not available from this repository. (Request a copy)Abstract
Immune-related adverse events (irAEs) in cancer patients receiving immune checkpoint inhibitors (ICIs) cause morbidity and necessitate cessation of treatment. Comparing irAE treatments, we find that anti-tumor immunity is preserved in mice after extracorporeal photopheresis (ECP) but reduced with glucocorticosteroids, TNFa blockade, and a4b7-integrin inhibition. Local adiponectin production elicits a tissue-specific effect by reducing pro-inflammatory T cell frequencies in the colon while sparing tumor-specific T cell development. A prospective phase-1b/2 trial (EudraCT-No.2021-002073-26) with 14 patients reveals low ECPrelated toxicity. Overall response rate for all irAEs is 92% (95% confidence interval [CI]: 63.97%-99.81%); colitis-specific complete remission rate is 100% (95% CI: 63.06%-100%). Glucocorticosteroid dosages could be reduced for all patients after ECP therapy. The ECP-adiponectin axis reduces intestinal tissue-resident memory T cell activation and CD4+IFN-g+ T cells in patients with ICI-induced colitis without evidence of loss of anti-tumor immunity. In conclusion, we identify adiponectin as an immunomodulatory molecule that controls ICI-induced irAEs without blocking anti-tumor immunity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; EXTRACORPOREAL PHOTOPHERESIS; MACROPHAGE POLARIZATION; INDUCED COLITIS; ADVERSE EVENTS; TNF-ALPHA; CELLS; IPILIMUMAB; MELANOMA; CANCER; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Abteilung für Nuklearmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Apr 2026 06:24 |
| Last Modified: | 20 Apr 2026 06:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67653 |
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