PMID- 24789737
OWN - NLM
STAT- MEDLINE
DCOM- 20141209
LR  - 20201226
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 135
IP  - 12
DP  - 2014 Dec 15
TI  - Lung tumours reprogram pulmonary dendritic cell immunogenicity at the microRNA 
      level.
PG  - 2868-77
LID - 10.1002/ijc.28945 [doi]
AB  - 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.
CI  - (c) 2014 UICC.
FAU - Pyfferoen, Lotte
AU  - Pyfferoen L
AD  - Department of Respiratory Medicine, Tumor Immunology Laboratory, Ghent University 
      Hospital, Ghent, Belgium; VIB Inflammation Research Center, Ghent, Belgium; 
      Department of Respiratory Medicine, Ghent University, Ghent, Belgium.
FAU - Mestdagh, Pieter
AU  - Mestdagh P
FAU - Vergote, Karl
AU  - Vergote K
FAU - De Cabooter, Nancy
AU  - De Cabooter N
FAU - Vandesompele, Jo
AU  - Vandesompele J
FAU - Lambrecht, Bart N
AU  - Lambrecht BN
FAU - Vermaelen, Karim Y
AU  - Vermaelen KY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140514
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-13)
RN  - 0 (Interleukin-17)
RN  - 0 (MIRN301 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.1.26.3 (DICER1 protein, human)
RN  - EC 3.1.26.3 (Ribonuclease III)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
SB  - IM
MH  - Animals
MH  - Antigens, Neoplasm/metabolism
MH  - Bone Marrow Cells/cytology
MH  - Cell Proliferation
MH  - Cytokines/metabolism
MH  - DEAD-box RNA Helicases/*metabolism
MH  - Dendritic Cells/*cytology
MH  - Gene Deletion
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Interleukin-12/metabolism
MH  - Interleukin-13/metabolism
MH  - Interleukin-17/metabolism
MH  - Lung Neoplasms/*immunology/therapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - MicroRNAs/*metabolism
MH  - Neoplasm Transplantation
MH  - Ribonuclease III/*metabolism
MH  - T-Lymphocytes, Cytotoxic/cytology/*metabolism
MH  - T-Lymphocytes, Helper-Inducer/cytology
OTO - NOTNLM
OT  - Dicer
OT  - dendritic cells
OT  - lung cancer
OT  - microRNAs
EDAT- 2014/05/03 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/05/03 06:00
PHST- 2013/11/26 00:00 [received]
PHST- 2014/04/15 00:00 [accepted]
PHST- 2014/05/03 06:00 [entrez]
PHST- 2014/05/03 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 10.1002/ijc.28945 [doi]
PST - ppublish
SO  - Int J Cancer. 2014 Dec 15;135(12):2868-77. doi: 10.1002/ijc.28945. Epub 2014 May 
      14.