Interleukin-10 overexpression in 4T1 cells: A gateway to suppressing mammary carcinoma growth.
Int Immunopharmacol
; 142(Pt A): 113089, 2024 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-39244897
ABSTRACT
Interleukin-10 (IL-10) exerts complex effects on tumor growth, exhibiting both pro- and anti-tumor properties. Recent focus on the anti-inflammatory properties of IL-10 has highlighted its potential anti-tumor properties, particularly through the enhancement of CD8+ T cell activity. However, further research is needed to fully elucidate its other anti-tumor mechanisms. Our study investigates novel anti-tumor mechanisms of IL-10 in a murine mammary carcinoma model (4T1). We found that IL-10 overexpression in mouse 4T1 cells suppressed tumor growth in vivo. This suppression was accompanied by an increase in IFN-γ-secreting CD8+ T cells and a decrease in myeloid-derived suppressor cells (MDSCs) in tumor tissue. In vitro experiments showed that IL-10-rich tumor cell-derived supernatants inhibited myeloid cell differentiation into monocytic and granulocytic MDSCs while reducing MDSCs migration. In addition, IL-10 overexpression downregulated CXCL5 expression in 4T1 cells, resulting in decreased CXCR2+ MDSCs infiltration. Using RAG1-deficient mice and CXCL5 knockdown tumor models, we demonstrated that the anti-tumor effects of IL-10 depend on both CD8+ T cells and reduced MDSC infiltration. IL-10 attenuated the immunosuppressive tumor microenvironment by enhancing CD8+ T cell activity and inhibiting MDSCs infiltration. In human breast cancer, we observed a positive correlation between CXCL5 expression and MDSC infiltration. Our findings reveal a dual mechanism of IL-10-mediated tumor suppression (1) direct enhancement of CD8+ T cell activity and (2) indirect reduction of immunosuppressive MDSCs through CXCL5 downregulation and inhibition of myeloid cell differentiation. This study provides new insights into the role of IL-10 in anti-tumor immunity and suggests potential strategies for breast cancer immunotherapy by modulating the IL-10-CXCL5-MDSCs axis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucina-10
/
Linfócitos T CD8-Positivos
/
Células Supressoras Mieloides
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Holanda