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Verfasst von:Schaper-Gerhardt, Katrin [VerfasserIn]   i
 Gutzmer, Ralf [VerfasserIn]   i
 Angela, Yenny [VerfasserIn]   i
 Zimmer, Lisa [VerfasserIn]   i
 Livingstone, Elisabeth [VerfasserIn]   i
 Schadendorf, Dirk [VerfasserIn]   i
 Hassel, Jessica C. [VerfasserIn]   i
 Weishaupt, Carsten [VerfasserIn]   i
 Remes, Bernhard [VerfasserIn]   i
 Kubat, Linda [VerfasserIn]   i
 Spassova, Ivelina [VerfasserIn]   i
 Becker, Jürgen C. [VerfasserIn]   i
Titel:The RANKL inhibitor denosumab in combination with dual checkpoint inhibition is associated with increased CXCL-13 serum concentrations
Verf.angabe:Katrin Schaper-Gerhardt, Ralf Gutzmer, Yenny Angela, Lisa Zimmer, Elisabeth Livingstone, Dirk Schadendorf, Jessica C. Hassel, Carsten Weishaupt, Bernhard Remes, Linda Kubat, Ivelina Spassova, Jürgen C. Becker
E-Jahr:2024
Jahr:2 March 2024
Umfang:9 S.
Illustrationen:Illustrationen
Fussnoten:Gesehen am 25.03.2025
Titel Quelle:Enthalten in: European journal of cancer
Ort Quelle:Amsterdam [u.a.] : Elsevier, 1992
Jahr Quelle:2024
Band/Heft Quelle:202(2024) vom: Mai, Artikel-ID 113984, Seite 1-9
ISSN Quelle:1879-0852
Abstract:BACKGROUND: Recent evidence suggests additional immunomodulatory properties of RANKL inhibition possibly boosting the clinical efficacy of immune checkpoint inhibitors (ICI). - METHODS: We conducted a prospective, multicentre clinical trial in unresectable stage IV melanoma patients with bone metastases who received denosumab in parallel with dual ICI (BONEMET) and performed comprehensive immune monitoring at baseline and 4, 12, and 24 weeks after initiation of therapy. Secondary endpoints included tolerability and efficacy. For comparison, biospecimens from melanoma patients treated with dual ICI without denosumab were analyzed accordingly and served as retrospective reference cohort. - RESULTS: In both the BONEMET (n = 16) and the reference cohort (n = 18) serum levels of 17 cytokines, including IFNγ were significantly increased after 4 weeks of treatment. Patients who received ICI and denosumab showed a significantly higher increase in serum CXCL-13 and a significant decrease in VEGFc compared with the reference cohort. While no changes in T cell composition were observed at 4 weeks, patients in the BONEMET cohort showed a significant decrease in the peripheral naïve T-cell population and an increase in CD8+ effector cells after 12 weeks. Treatment-related adverse events occurred with comparable frequency (93.8% in the BONEMET cohort versus 83.3% in the reference cohort). 7/16 patients in the BONEMET cohort and 8/18 patients in the reference cohort achieved disease control. - CONCLUSION: Denosumab in combination with dual ICI modulates cytokine expression and T-cell composition in peripheral blood. The upregulation of CXCL-13, a key factor for initiating tertiary lymphoid structures, strengthens the hypothesis that denosumab indeed boost immunological effects.
DOI:doi:10.1016/j.ejca.2024.113984
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: https://doi.org/10.1016/j.ejca.2024.113984
 kostenfrei: Volltext: https://www.sciencedirect.com/science/article/pii/S0959804924001400?via%3Dihub
 DOI: https://doi.org/10.1016/j.ejca.2024.113984
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Bone Neoplasms
 CXCL-13
 Cytokines
 Denosumab
 Humans
 Immunotherapy
 Melanoma
 Prospective Studies
 RANKL
 Retrospective Studies
 T-Lymphocytes
K10plus-PPN:1920524959
Verknüpfungen:→ Zeitschrift

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