PMID- 28197369
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 2162-4011 (Print)
IS  - 2162-402X (Electronic)
IS  - 2162-4011 (Linking)
VI  - 6
IP  - 1
DP  - 2017
TI  - The transcriptome of lung tumor-infiltrating dendritic cells reveals a 
      tumor-supporting phenotype and a microRNA signature with negative impact on 
      clinical outcome.
PG  - e1253655
LID - 10.1080/2162402X.2016.1253655 [doi]
LID - e1253655
AB  - Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. 
      Further progress requires deeper insights into the biology of immune cells in the 
      lung cancer micro-environment. Dendritic cells (DCs) represent a heterogeneous 
      and highly plastic immune cell system with a central role in controlling immune 
      responses. The intratumoral infiltration and activation status of DCs are 
      emerging as clinically relevant parameters in lung cancer. In this study, we used 
      an orthotopic preclinical model of lung cancer to dissect how the lung tumor 
      micro-environment affects tissue-resident DCs and extract novel biologically and 
      clinically relevant information. Lung tumor-infiltrating leukocytes expressing 
      generic DC markers were found to predominantly consist of CD11b(+) cells that, 
      compare with peritumoral lung DC counterparts, strongly overexpress the T-cell 
      inhibitory molecule PD-L1 and acquire classical surface markers of 
      tumor-associated macrophages (TAMs). Transcriptome analysis of these CD11b(+) 
      tumor-infiltrating DCs (TIDCs) indicates impaired antitumoral immunogenicity, 
      confirms the skewing toward TAM-related features, and indicates exposure to a 
      hypoxic environment. In parallel, TIDCs display a specific microRNA (miRNA) 
      signature dominated by the prototypical lung cancer oncomir miR-31. In vitro, 
      hypoxia drives intrinsic miR-31 expression in CD11b(+) DCs. Conditioned medium of 
      miR-31 overexpressing CD11b(+) DCs induces pro-invasive lung cancer cell shape 
      changes and is enriched with pro-metastatic soluble factors. Finally, analysis of 
      TCGA datasets reveals that the TIDC-associated miRNA signature has a negative 
      prognostic impact in non-small cell lung cancer. Together, these data suggest a 
      novel mechanism through which the lung cancer micro-environment exploits the 
      plasticity of the DC system to support tumoral progression.
FAU - Pyfferoen, Lotte
AU  - Pyfferoen L
AD  - Tumor Immunology Laboratory, Department of Respiratory Medicine, Ghent University 
      Hospital, Ghent, Belgium; VIB Inflammation Research Center, Ghent, Belgium.
FAU - Brabants, Elisabeth
AU  - Brabants E
AD  - Tumor Immunology Laboratory, Department of Respiratory Medicine, Ghent University 
      Hospital , Ghent, Belgium.
FAU - Everaert, Celine
AU  - Everaert C
AD  - Center for Medical Genetics, Ghent University , Ghent, Belgium.
FAU - De Cabooter, Nancy
AU  - De Cabooter N
AD  - Tumor Immunology Laboratory, Department of Respiratory Medicine, Ghent University 
      Hospital , Ghent, Belgium.
FAU - Heyns, Kelly
AU  - Heyns K
AD  - Tumor Immunology Laboratory, Department of Respiratory Medicine, Ghent University 
      Hospital , Ghent, Belgium.
FAU - Deswarte, Kim
AU  - Deswarte K
AD  - VIB Inflammation Research Center , Ghent, Belgium.
FAU - Vanheerswynghels, Manon
AU  - Vanheerswynghels M
AD  - VIB Inflammation Research Center , Ghent, Belgium.
FAU - De Prijck, Sofie
AU  - De Prijck S
AD  - VIB Inflammation Research Center , Ghent, Belgium.
FAU - Waegemans, Glenn
AU  - Waegemans G
AD  - Laboratory of Experimental Cancer Research, Ghent University , Ghent, Belgium.
FAU - Dullaers, Melissa
AU  - Dullaers M
AD  - Tumor Immunology Laboratory, Department of Respiratory Medicine, Ghent University 
      Hospital, Ghent, Belgium; VIB Inflammation Research Center, Ghent, Belgium.
FAU - Hammad, Hamida
AU  - Hammad H
AD  - VIB Inflammation Research Center , Ghent, Belgium.
FAU - De Wever, Olivier
AU  - De Wever O
AD  - Laboratory of Experimental Cancer Research, Ghent University , Ghent, Belgium.
FAU - Mestdagh, Pieter
AU  - Mestdagh P
AD  - Center for Medical Genetics, Ghent University , Ghent, Belgium.
FAU - Vandesompele, Jo
AU  - Vandesompele J
AD  - Center for Medical Genetics, Ghent University , Ghent, Belgium.
FAU - Lambrecht, Bart N
AU  - Lambrecht BN
AD  - VIB Inflammation Research Center, Ghent, Belgium; Department of Pulmonary 
      Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, the 
      Netherlands.
FAU - Vermaelen, Karim Y
AU  - Vermaelen KY
AD  - Tumor Immunology Laboratory, Department of Respiratory Medicine, Ghent University 
      Hospital , Ghent, Belgium.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161108
PL  - United States
TA  - Oncoimmunology
JT  - Oncoimmunology
JID - 101570526
PMC - PMC5283643
OTO - NOTNLM
OT  - Dendritic cell
OT  - PD-L1
OT  - hypoxia
OT  - lung cancer
OT  - miR-31
EDAT- 2017/02/16 06:00
MHDA- 2017/02/16 06:01
PMCR- 2016/11/08
CRDT- 2017/02/16 06:00
PHST- 2016/08/10 00:00 [received]
PHST- 2016/09/23 00:00 [revised]
PHST- 2016/10/24 00:00 [accepted]
PHST- 2017/02/16 06:00 [entrez]
PHST- 2017/02/16 06:00 [pubmed]
PHST- 2017/02/16 06:01 [medline]
PHST- 2016/11/08 00:00 [pmc-release]
AID - 1253655 [pii]
AID - 10.1080/2162402X.2016.1253655 [doi]
PST - epublish
SO  - Oncoimmunology. 2016 Nov 8;6(1):e1253655. doi: 10.1080/2162402X.2016.1253655. 
      eCollection 2017.