Title :

Pc1/3 kd macrophages exhibit resistance to the inhibitory effect of il-10 and a higher tlr4 activation rate, leading to an anti-tumoral phenotype

Author(s) :

Rodet, Franck [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Capuz, Alice [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Ozcan, Bilgehan-Aybike [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Le Beillan, Remy [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Raffo Romero, Antonella [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Kobeissy, Firas [Auteur]
The University of Florida College of Medicine
Duhamel, Marie [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Salzet, Michel [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Journal title :

Cells

Abbreviated title :

Cells

Volume number :

8

Pages :

1490

Publisher :

MDPI

Publication date :

2019-11-22

ISSN :

2073-4409

Keyword(s) :

anti-tumoral immunotherapy
proprotein convertase 1/3
TLR4 desensitization
IL-10 pro-tumoral effect
macrophages

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

During tumorigenesis, macrophages are recruited by tumors and orientated towards a pro-tumoral phenotype. One of the main anti-tumoral immunotherapy consists of their re-polarization in an anti-tumoral phenotype. We have ...
Show more >During tumorigenesis, macrophages are recruited by tumors and orientated towards a pro-tumoral phenotype. One of the main anti-tumoral immunotherapy consists of their re-polarization in an anti-tumoral phenotype. We have demonstrated that the inhibition of proprotein convertase 1/3 combined with TLR4 activation in macrophages is a promising strategy. These macrophages display pro-inflammatory and anti-tumoral phenotypes. A hallmark is a stronger activation of the pro-inflammatory NFKB pathway. We believe that this can be explained by a modification of TLR4 expression at the cell surface or MYD88 cleavage since it exhibits a potential cleavage site for proprotein convertases. We tested these hypotheses through immunofluorescence and Western blot experiments. A proteomics study was also performed to test the sensitivity of these macrophages to IL-10. We demonstrated that these macrophages treated with LPS showed a quicker re-expression of TLR4 at the cell surface. The level of MYD88 was also higher when TLR4 was internalized. Moreover, these macrophages were resistant to the pro-tumoral effect of IL-10 and still produced pro-inflammatory factors. This established that the sensitivity to anti-inflammatory molecules and the length of TLR4 desensitization were reduced in these macrophages. Therefore, during antitumoral immunotherapy, a repeated stimulation of TLR4 may reactivate PC1/3 inhibited macrophages even in an anti-inflammatory environment.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

INSERM
Université de Lille

Collections :

• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Submission date :

2022-06-15T13:59:14Z
2023-02-01T09:23:48Z