Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer.
Gastric Cancer
; 27(2): 248-262, 2024 03.
Article
em En
| MEDLINE
| ID: mdl-38217732
ABSTRACT
BACKGROUND:
Gastric cancer (GC) is characterized by an immunosuppressive and treatment-resistant tumor immune microenvironment (TIME). Here, we investigated the roles of different immunosuppressive cell types in the development of the GC TIME.METHODS:
Single-cell RNA sequencing (scRNA-seq) and multiplex immunostaining of samples from untreated or immune checkpoint inhibitor (ICI)-resistant GC patients were used to examine the correlation between certain immunosuppressive cells and the prognosis of GC patients.RESULTS:
The results of the scRNA-seq analysis revealed that tumor-infiltrating monocytic myeloid-derived suppressor cells (TI-M-MDSCs) expressed higher levels of genes with immunosuppressive functions than other immunosuppressive cell types. Additionally, M-MDSCs in GC tissues expressed significantly higher levels of these markers than adjacent normal tissues. The M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues. Among the immunosuppressive cell types assessed, the M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues; moreover, their presence was most strongly associated with a poor prognosis. Immediate early response 3 (IER3), which we identified as a differentially expressed gene between M-MDSCs of GC and adjacent normal tissues, was an independent poor prognostic factor in GC patients (P = 0.0003). IER3+ M-MDSCs expressed higher levels of genes with immunosuppressive functions than IER3- M-MDSCs and were abundant in treatment-resistant GC patients.CONCLUSIONS:
The present study suggests that TI-M-MDSCs, especially IER3+ ones, may play a predominant role in the development of the immunosuppressive and ICI-resistant GC TIME.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Células Supressoras Mieloides
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Gastric Cancer
Ano de publicação:
2024
Tipo de documento:
Article