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

Details

Serval ID
serval:BIB_F08435B3AEB3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Loss of MAPK-activated protein kinase 2 enables potent dendritic cell-driven anti-tumour T cell response.
Journal
Scientific reports
Author(s)
Soukup K., Halfmann A., Dillinger B., Poyer F., Martin K., Blauensteiner B., Kauer M., Kuttke M., Schabbauer G., Dohnal A.M.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
18/09/2017
Peer-reviewed
Oui
Volume
7
Number
1
Pages
11746
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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 <sup>+</sup> cells led to an expansion of stimulatory CD103 <sup>+</sup> DCs, mounting a potent CD8 <sup>+</sup> 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.
Keywords
Animals, CD8-Positive T-Lymphocytes/enzymology, CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/pathology, Cell Line, Tumor, Dendritic Cells/enzymology, Dendritic Cells/immunology, Dendritic Cells/pathology, Immunity, Cellular, Intracellular Signaling Peptides and Proteins/deficiency, Intracellular Signaling Peptides and Proteins/immunology, Melanoma, Experimental/enzymology, Melanoma, Experimental/genetics, Melanoma, Experimental/immunology, Melanoma, Experimental/pathology, Mice, Mice, Knockout, Protein-Serine-Threonine Kinases/deficiency, Protein-Serine-Threonine Kinases/immunology, Tumor Microenvironment/genetics, Tumor Microenvironment/immunology
Pubmed
Web of science
Open Access
Yes
Create date
13/10/2017 17:29
Last modification date
20/08/2019 17:18
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