Adiponectin reduces immune checkpoint inhibitor-induced inflammation without blocking anti-tumor immunity

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, TNFα blockade, and α4β7-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 ECP-related 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-γ+ 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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Cancer cell. - 43, 2 (2025) , 269-291, ISSN: 1878-3686

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2025
• Creator: Braun, Lukas M. ; Giesler, Sophie ; Geoffroy, Andrieux ; Riemer, Roxane ; Talvard-Balland, Nana ; Duquesne, Sandra ; Rückert, Tamina ; Zwick, Melissa ; Follo, Marie ; Hartmann, Alina ; Osswald, Natascha ; Melchinger, Wolfgang ; Chapman, Stefanie ; Karantzelis, Nikolaos ; Wallrabenstein, Till ; Lowinus, Theresa ; Yücel, Mehtap ; Brehm, Niklas ; Rawluk, Justyna ; Pfeifer, Dietmar ; Bronsert, Peter ; Rogg, Manuel ; Schmitt-Graeff, Annette ; Börries, Melanie ; Köhler, Natalie ; Duyster, Justus ; Ihorst, Gabriele ; Laßmann, Silke ; Keye, Philip ; Minguet, Susana ; Rafei-Shamsabadi, David Ali ; Thimme, Robert ; Hasselblatt, Peter ; Bengsch, Bertram ; Schell, Christoph ; Meiß, Frank ; Apostolova, Petya ; Zeiser, Robert

Further information

• DOI: 10.1016/j.ccell.2025.01.004
• URN: urn:nbn:de:bsz:25-freidok-2630176
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:28 AM CEST