Document Detail


Lung tumours reprogram pulmonary dendritic cell immunogenicity at the microRNA level.
MedLine Citation:
PMID:  24789737     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Lung cancer arises in a context of tumour-induced immune suppression. Dendritic cells (DCs) are central players in the induction of anti-tumoural immunity, providing critical signals that drive the induction of cytotoxic T-cell responses. Meanwhile, microRNAs are associated with tumour development as well as immune regulation. We postulated that lung tumours escape immune control by reprogramming DC immunogenicity at the microRNA level. Using an orthotopic model of lung cancer, we first identified the DC population responsible for transport and cross-presentation of lung tumour-derived antigens to naïve T cells in the draining mediastinal lymph nodes (LNs). Profiling the full microRNA repertoire of these DCs revealed a restricted set of microRNAs that was consistently dysregulated in the presence of lung tumours, with miR-301a as one of the top upregulated transcripts. Overexpression of miR-301a in DCs suppressed IL-12 secretion, decreased IFN-γ release from antigen-specific cytotoxic T cells, and shifted antigen-specific T helper cytokine profile away from IFN-γ towards IL-13 and IL-17A-secreting T cells. Strikingly, DC-selective Dicer1 gene deletion resulted in delayed lung tumour growth and a survival benefit. Taken together, our data reveal that lung tumours induce an immunosuppressive microRNA signature in pulmonary DCs. Interfering with the DC-intrinsic capacity to remodel microRNA repertoires affects lung tumour outcome. © 2014 Wiley Periodicals, Inc.
Authors:
Lotte Pyfferoen; Pieter Mestdagh; Karl Vergote; Nancy De Cabooter; Jo Vandesompele; Bart N Lambrecht; Karim Y Vermaelen
Related Documents :
11068857 - Molecular mechanisms of uv-induced apoptosis.
24027317 - Kaposi's sarcoma-associated herpesvirus k7 modulates rubicon-mediated inhibition of aut...
19392987 - Impaired tlr-2 expression and tlr-2-mediated cytokine secretion in macrophages from pat...
17999197 - Targeted disruption of the galanin gene attenuates inflammatory responses in murine skin.
24252697 - Polysaccharides from ganoderma formosanum function as a th1 adjuvant and stimulate cyto...
17804237 - Ros, mitochondria and the regulation of autophagy.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-5-2
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-5-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 UICC.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Using problem solving therapy to treat veterans with subsyndromal depression: a pilot study.
Next Document:  High dose alkylator therapy for extracranial malignant rhabdoid tumors in children.