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

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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

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Cancer cell. - 43, 2 (2025) , 269-291, ISSN: 1878-3686

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2025
Urheber

DOI
10.1016/j.ccell.2025.01.004
URN
urn:nbn:de:bsz:25-freidok-2630176
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:28 MESZ

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