CD45+CD33lowCD11bdim myeloid-derived suppressor cells suppress CD8+ T cell activity via the IL-6/IL-8-arginase I axis in human gastric cancer.
Cell Death Dis
; 9(7): 763, 2018 07 09.
Article
em En
| MEDLINE
| ID: mdl-29988030
ABSTRACT
Myeloid-derived suppressor cells (MDSCs) are a prominent component of the pro-tumoral response. The phenotype of and mechanisms used by MDSCs is heterogeneous and requires more precise characterization in gastric cancer (GC) patients. Here, we have identified a novel subset of CD45+CD33lowCD11bdim MDSCs in the peripheral blood of GC patients compared to healthy individuals. CD45+CD33lowCD11bdim MDSCs morphologically resembled neutrophils and expressed high levels of the neutrophil marker CD66b. Circulating CD45+CD33lowCD11bdim MDSCs effectively suppressed CD8+ T cells activity through the inhibition of CD8+ T cell proliferation and interferon-γ (IFN-γ) and granzyme B (GrB) production. The proportion of CD45+CD33lowCD11bdim MDSCs also negatively correlated with the proportion of IFN-γ+CD8+ T cell in the peripheral blood of GC patients. GC patient serum-derived IL-6 and IL-8 activated and induced CD45+CD33lowCD11bdim MDSCs to express arginase I via the PI3K-AKT signaling pathway. This pathway contributed to CD8+ T cell suppression as it was partially rescued by the blockade of the IL-6/IL-8-arginase I axis. Peripheral blood CD45+CD33lowCD11bdim MDSCs, as well as IL-6, IL-8, and arginase I serum levels, positively correlated with GC progression and negatively correlated with overall patient survival. Altogether, our results highlight that a subset of neutrophilic CD45+CD33lowCD11bdim MDSCs is functionally immunosuppressive and activated via the IL-6/IL-8-arginase I axis in GC patients.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Arginase
/
Neoplasias Gástricas
/
Antígenos Comuns de Leucócito
/
Linfócitos T CD8-Positivos
/
Antígeno CD11b
/
Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico
/
Células Supressoras Mieloides
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article