Melanoma patients with immune-related adverse events after immune checkpoint inhibitors are characterized by a distinct immunological phenotype of circulating T cells and M-MDSCs

• Verfasst von: Lepper, Alisa [VerfasserIn]
• Verfasst von: Weber, Rebekka [VerfasserIn]
• Verfasst von: Özbay Kurt, Feyza Gül [VerfasserIn]
• Verfasst von: Arkhypov, Ihor [VerfasserIn]
• Verfasst von: Lasser, Samantha [VerfasserIn]
• Verfasst von: Utikal, Jochen [VerfasserIn]
• Verfasst von: Umansky, Viktor [VerfasserIn]
• Titel: Melanoma patients with immune-related adverse events after immune checkpoint inhibitors are characterized by a distinct immunological phenotype of circulating T cells and M-MDSCs
• Titelzusatz: original research
• Verf.angabe: Alisa Lepper, Rebekka Bitsch, Feyza Gül Özbay Kurt, Ihor Arkhypov, Samantha Lasser, Jochen Utikal, and Viktor Umansky
• E-Jahr: 2023
• Jahr: 13 Aug 2023
• Umfang: 9 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 16.04.2024
• Titel Quelle: Enthalten in: OncoImmunology
• Ort Quelle: Abingdon : Taylor & Franics, 2012
• Jahr Quelle: 2023
• Band/Heft Quelle: 12(2023), 1, Seite 1-9
• ISSN Quelle: 2162-402X
• DOI: doi:10.1080/2162402X.2023.2247303
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Immune-related adverse events
• Sach-SW: immunotherapy
• Sach-SW: melanoma
• K10plus-PPN: 1885917082

Abstract

Treatment with immune checkpoint inhibitors (ICIs) has improved the prognosis of melanoma patients. However, ICIs can cause an overactivation of the immune system followed by diverse immunological side effects known as immune-related adverse events (irAE). Currently, the toxicity of irAE is limiting the usage of ICIs. Here, we studied circulating monocytic myeloid-derived suppressor cells (M-MDSCs) and T cells in course of irAE after the ICI therapy. Our longitudinal study involved 31 melanoma patients with and without adverse events during anti-PD-1 monotherapy or anti-CTLA-4/PD-1 combination therapy. Peripheral blood samples were analyzed before ICI start, during ICI treatment, at the time point of irAE and during immunosuppressive treatment to cure irAE. We observed an enhanced progression-free survival among patients with irAE. In patients with irAE, we found an upregulation of CD69 on CD8+ T cells and a decreased frequency of regulatory T cells (Tregs). Moreover, lower frequencies of Tregs correlated with more severe side effects. Patients treated with immunomodulatory drugs after irAE manifestation tend to show an elevated number of M-MDSCs during an immunosuppressive therapy. We suggest that an activation of CD8+ T cells and the reduction of Treg frequencies could be responsible for the development of irAE.