CD8+ T cells inhibit metastasis and CXCL4 regulates its function.
Br J Cancer
; 125(2): 176-189, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-33795809
ABSTRACT
BACKGROUND:
The mechanism by which immune cells regulate metastasis is unclear. Understanding the role of immune cells in metastasis will guide the development of treatments improving patient survival.METHODS:
We used syngeneic orthotopic mouse tumour models (wild-type, NOD/scid and Nude), employed knockout (CD8 and CD4) models and administered CXCL4. Tumours and lungs were analysed for cancer cells by bioluminescence, and circulating tumour cells were isolated from blood. Immunohistochemistry on the mouse tumours was performed to confirm cell type, and on a tissue microarray with 180 TNBCs for human relevance. TCGA data from over 10,000 patients were analysed as well.RESULTS:
We reveal that intratumoral immune infiltration differs between metastatic and non-metastatic tumours. The non-metastatic tumours harbour high levels of CD8+ T cells and low levels of platelets, which is reverse in metastatic tumours. During tumour progression, platelets and CXCL4 induce differentiation of monocytes into myeloid-derived suppressor cells (MDSCs), which inhibit CD8+ T-cell function. TCGA pan-cancer data confirmed that CD8lowPlatelethigh patients have a significantly lower survival probability compared to CD8highPlateletlow.CONCLUSIONS:
CD8+ T cells inhibit metastasis. When the balance between CD8+ T cells and platelets is disrupted, platelets produce CXCL4, which induces MDSCs thereby inhibiting the CD8+ T-cell function.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Pulmao
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Fator Plaquetário 4
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Antígenos CD4
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Antígenos CD8
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Linfócitos T CD8-Positivos
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Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos