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Lung tumours reprogram pulmonary dendritic cell immunogenicity at the microRNA level

Lotte Pyfferoen, Pieter Mestdagh UGent, Karl Vergote UGent, Nancy De Cabooter, Jo Vandesompele UGent, Bart Lambrecht UGent and Karim Vermaelen UGent (2014) INTERNATIONAL JOURNAL OF CANCER. 135(12). p.2868-2877
abstract
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 naive 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-gamma release from antigen-specific cytotoxic T cells, and shifted antigen-specific T helper cytokine profile away from IFN-gamma 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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
dendritic cells, lung cancer, microRNAs, Dicer, CD4(+) T-CELLS, INTRATRACHEAL INSTILLATION, IMMUNE-RESPONSES, LYMPH-NODES, CANCER, ANTIGEN, ACTIVATION, MIRNA, TUMORIGENESIS, GENERATION
journal title
INTERNATIONAL JOURNAL OF CANCER
Int. J. Cancer
volume
135
issue
12
pages
2868 - 2877
Web of Science type
Article
Web of Science id
000343055600013
JCR category
ONCOLOGY
JCR impact factor
5.085 (2014)
JCR rank
31/211 (2014)
JCR quartile
1 (2014)
ISSN
0020-7136
DOI
10.1002/ijc.28945
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
5708661
handle
http://hdl.handle.net/1854/LU-5708661
date created
2014-09-24 09:32:18
date last changed
2016-12-19 15:42:18
@article{5708661,
  abstract     = {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 naive 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-gamma release from antigen-specific cytotoxic T cells, and shifted antigen-specific T helper cytokine profile away from IFN-gamma 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.},
  author       = {Pyfferoen, Lotte and Mestdagh, Pieter and Vergote, Karl and De Cabooter, Nancy and Vandesompele, Jo and Lambrecht, Bart and Vermaelen, Karim},
  issn         = {0020-7136},
  journal      = {INTERNATIONAL JOURNAL OF CANCER},
  keyword      = {dendritic cells,lung cancer,microRNAs,Dicer,CD4(+) T-CELLS,INTRATRACHEAL INSTILLATION,IMMUNE-RESPONSES,LYMPH-NODES,CANCER,ANTIGEN,ACTIVATION,MIRNA,TUMORIGENESIS,GENERATION},
  language     = {eng},
  number       = {12},
  pages        = {2868--2877},
  title        = {Lung tumours reprogram pulmonary dendritic cell immunogenicity at the microRNA level},
  url          = {http://dx.doi.org/10.1002/ijc.28945},
  volume       = {135},
  year         = {2014},
}

Chicago
Pyfferoen, Lotte, Pieter Mestdagh, Karl Vergote, NANCY DE CABOOTER, Jo Vandesompele, Bart Lambrecht, and Karim Vermaelen. 2014. “Lung Tumours Reprogram Pulmonary Dendritic Cell Immunogenicity at the microRNA Level.” International Journal of Cancer 135 (12): 2868–2877.
APA
Pyfferoen, L., Mestdagh, P., Vergote, K., DE CABOOTER, N., Vandesompele, J., Lambrecht, B., & Vermaelen, K. (2014). Lung tumours reprogram pulmonary dendritic cell immunogenicity at the microRNA level. INTERNATIONAL JOURNAL OF CANCER, 135(12), 2868–2877.
Vancouver
1.
Pyfferoen L, Mestdagh P, Vergote K, DE CABOOTER N, Vandesompele J, Lambrecht B, et al. Lung tumours reprogram pulmonary dendritic cell immunogenicity at the microRNA level. INTERNATIONAL JOURNAL OF CANCER. 2014;135(12):2868–77.
MLA
Pyfferoen, Lotte, Pieter Mestdagh, Karl Vergote, et al. “Lung Tumours Reprogram Pulmonary Dendritic Cell Immunogenicity at the microRNA Level.” INTERNATIONAL JOURNAL OF CANCER 135.12 (2014): 2868–2877. Print.