Loss of MAPK-activated protein kinase 2 enables potent dendritic cell-driven anti-tumour T cell response

Abstract Maintaining dendritic cells (DC) in a state of dysfunction represents a key mechanism by which tumour cells evade recognition and elimination by the immune system. Limited knowledge about the intracellular mediators of DC dysfunction restricts success of therapies aimed at reactivating a DC...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Klara Soukup, Angela Halfmann, Barbara Dillinger, Fiona Poyer, Katharina Martin, Bernadette Blauensteiner, Maximilian Kauer, Mario Kuttke, Gernot Schabbauer, Alexander M. Dohnal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3fe0c65fdfaf40938ede05519f522fc0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3fe0c65fdfaf40938ede05519f522fc0
record_format	dspace
spelling	oai:doaj.org-article:3fe0c65fdfaf40938ede05519f522fc02021-12-02T11:50:55ZLoss of MAPK-activated protein kinase 2 enables potent dendritic cell-driven anti-tumour T cell response10.1038/s41598-017-12208-72045-2322https://doaj.org/article/3fe0c65fdfaf40938ede05519f522fc02017-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-12208-7https://doaj.org/toc/2045-2322Abstract Maintaining dendritic cells (DC) in a state of dysfunction represents a key mechanism by which tumour cells evade recognition and elimination by the immune system. Limited knowledge about the intracellular mediators of DC dysfunction restricts success of therapies aimed at reactivating a DC-driven anti-tumour immune response. Using a cell type-specific murine knock-out model, we have identified MAPK-activated protein kinase 2 (MK2) as a major guardian of a suppressive DC phenotype in the melanoma tumour microenvironment. MK2 deletion in CD11c+ cells led to an expansion of stimulatory CD103+ DCs, mounting a potent CD8+ T cell response that resulted in elimination of highly aggressive B16-F10 tumours upon toll-like receptor (TLR) activation in the presence of tumour antigen. Moreover, tumour infiltration by suppressive myeloid cells was strongly diminished. These insights into the regulation of DC functionality reveal MK2 as a targetable pathway for DC-centred immunomodulatory cancer therapies.Klara SoukupAngela HalfmannBarbara DillingerFiona PoyerKatharina MartinBernadette BlauensteinerMaximilian KauerMario KuttkeGernot SchabbauerAlexander M. DohnalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Klara Soukup Angela Halfmann Barbara Dillinger Fiona Poyer Katharina Martin Bernadette Blauensteiner Maximilian Kauer Mario Kuttke Gernot Schabbauer Alexander M. Dohnal Loss of MAPK-activated protein kinase 2 enables potent dendritic cell-driven anti-tumour T cell response
description	Abstract Maintaining dendritic cells (DC) in a state of dysfunction represents a key mechanism by which tumour cells evade recognition and elimination by the immune system. Limited knowledge about the intracellular mediators of DC dysfunction restricts success of therapies aimed at reactivating a DC-driven anti-tumour immune response. Using a cell type-specific murine knock-out model, we have identified MAPK-activated protein kinase 2 (MK2) as a major guardian of a suppressive DC phenotype in the melanoma tumour microenvironment. MK2 deletion in CD11c+ cells led to an expansion of stimulatory CD103+ DCs, mounting a potent CD8+ T cell response that resulted in elimination of highly aggressive B16-F10 tumours upon toll-like receptor (TLR) activation in the presence of tumour antigen. Moreover, tumour infiltration by suppressive myeloid cells was strongly diminished. These insights into the regulation of DC functionality reveal MK2 as a targetable pathway for DC-centred immunomodulatory cancer therapies.
format	article
author	Klara Soukup Angela Halfmann Barbara Dillinger Fiona Poyer Katharina Martin Bernadette Blauensteiner Maximilian Kauer Mario Kuttke Gernot Schabbauer Alexander M. Dohnal
author_facet	Klara Soukup Angela Halfmann Barbara Dillinger Fiona Poyer Katharina Martin Bernadette Blauensteiner Maximilian Kauer Mario Kuttke Gernot Schabbauer Alexander M. Dohnal
author_sort	Klara Soukup
title	Loss of MAPK-activated protein kinase 2 enables potent dendritic cell-driven anti-tumour T cell response
title_short	Loss of MAPK-activated protein kinase 2 enables potent dendritic cell-driven anti-tumour T cell response
title_full	Loss of MAPK-activated protein kinase 2 enables potent dendritic cell-driven anti-tumour T cell response
title_fullStr	Loss of MAPK-activated protein kinase 2 enables potent dendritic cell-driven anti-tumour T cell response
title_full_unstemmed	Loss of MAPK-activated protein kinase 2 enables potent dendritic cell-driven anti-tumour T cell response
title_sort	loss of mapk-activated protein kinase 2 enables potent dendritic cell-driven anti-tumour t cell response
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3fe0c65fdfaf40938ede05519f522fc0
work_keys_str_mv	AT klarasoukup lossofmapkactivatedproteinkinase2enablespotentdendriticcelldrivenantitumourtcellresponse AT angelahalfmann lossofmapkactivatedproteinkinase2enablespotentdendriticcelldrivenantitumourtcellresponse AT barbaradillinger lossofmapkactivatedproteinkinase2enablespotentdendriticcelldrivenantitumourtcellresponse AT fionapoyer lossofmapkactivatedproteinkinase2enablespotentdendriticcelldrivenantitumourtcellresponse AT katharinamartin lossofmapkactivatedproteinkinase2enablespotentdendriticcelldrivenantitumourtcellresponse AT bernadetteblauensteiner lossofmapkactivatedproteinkinase2enablespotentdendriticcelldrivenantitumourtcellresponse AT maximiliankauer lossofmapkactivatedproteinkinase2enablespotentdendriticcelldrivenantitumourtcellresponse AT mariokuttke lossofmapkactivatedproteinkinase2enablespotentdendriticcelldrivenantitumourtcellresponse AT gernotschabbauer lossofmapkactivatedproteinkinase2enablespotentdendriticcelldrivenantitumourtcellresponse AT alexandermdohnal lossofmapkactivatedproteinkinase2enablespotentdendriticcelldrivenantitumourtcellresponse
_version_	1718395158652780544

Loss of MAPK-activated protein kinase 2 enables potent dendritic cell-driven anti-tumour T cell response

Ejemplares similares