Neutrophils suppress tumor-infiltrating T cells in colon cancer via matrix metalloproteinase-mediated activation of TGFß.
EMBO Mol Med
; 12(1): e10681, 2020 01 09.
Article
en En
| MEDLINE
| ID: mdl-31793740
ABSTRACT
High T-cell infiltration in colorectal cancer (CRC) correlates with a favorable disease outcome and immunotherapy response. This, however, is only observed in a small subset of CRC patients. A better understanding of the factors influencing tumor T-cell responses in CRC could inspire novel therapeutic approaches to achieve broader immunotherapy responsiveness. Here, we investigated T cell-suppressive properties of different myeloid cell types in an inducible colon tumor mouse model. The most potent inhibitors of T-cell activity were tumor-infiltrating neutrophils. Gene expression analysis and combined in vitro and in vivo tests indicated that T-cell suppression is mediated by neutrophil-secreted metalloproteinase activation of latent TGFß. CRC patient neutrophils similarly suppressed T cells via TGFß in vitro, and public gene expression datasets suggested that T-cell activity is lowest in CRCs with combined neutrophil infiltration and TGFß activation. Thus, the interaction of neutrophils with a TGFß-rich tumor microenvironment may represent a conserved immunosuppressive mechanism in CRC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T
/
Linfocitos Infiltrantes de Tumor
/
Factor de Crecimiento Transformador beta
/
Neoplasias del Colon
/
Metaloproteinasas de la Matriz
/
Neutrófilos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
EMBO Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2020
Tipo del documento:
Article
País de afiliación:
Suiza