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.
Oncoimmunology
; 12(1): 2247303, 2023.
Article
en En
| MEDLINE
| ID: mdl-37593676
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Células Supresoras de Origen Mieloide
/
Melanoma
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Oncoimmunology
Año:
2023
Tipo del documento:
Article
País de afiliación:
Alemania