PMID- 26010746
OWN - NLM
STAT- MEDLINE
DCOM- 20160930
LR  - 20181113
IS  - 1440-1711 (Electronic)
IS  - 0818-9641 (Linking)
VI  - 94
IP  - 1
DP  - 2016 Jan
TI  - Melanoma-derived factors alter the maturation and activation of differentiated 
      tissue-resident dendritic cells.
PG  - 24-38
LID - 10.1038/icb.2015.58 [doi]
AB  - Dendritic cells (DCs) are key regulators of host immunity that are capable of 
      inducing either immune tolerance or activation. In addition to their 
      well-characterized role in shaping immune responses to foreign pathogens, DCs are 
      also known to be critical for the induction and maintenance of anti-tumor immune 
      responses. Therefore, it is important to understand how tumors influence the 
      function of DCs and the quality of immune responses they elicit. Although the 
      majority of studies in this field to date have utilized either immortalized DC 
      lines or DC populations that have been generated under artificial conditions from 
      hematopoietic precursors in vitro, we wished to investigate how tumors impact the 
      function of already differentiated, tissue-resident DCs. Therefore, we used both 
      an ex vivo and in vivo model system to assess the influence of melanoma-derived 
      factors on DC maturation and activation. In ex vivo studies with freshly isolated 
      splenic DCs, we demonstrate that the extent to which DC maturation and activation 
      are altered by these factors correlates with melanoma tumorigenicity, and we 
      identify partial roles for tumor-derived transforming growth factor (TGF)beta1 and 
      vascular endothelial growth factor (VEGF)-A in the altered functionality of DCs. 
      In vivo studies using a lung metastasis model of melanoma also demonstrate 
      tumorigenicity-dependent alterations to the function of lung-resident DCs, and 
      skewed production of proinflammatory cytokines and chemokines by these 
      tumor-altered cells is associated with recruitment of an immune infiltrate that 
      may ultimately favor tumor immune escape and outgrowth.
FAU - Hargadon, Kristian M
AU  - Hargadon KM
AD  - Hargadon Laboratory, Department of Biology, Hampden-Sydney College, 
      Hampden-Sydney, VA, USA.
FAU - Bishop, Johnathan D
AU  - Bishop JD
AD  - Hargadon Laboratory, Department of Biology, Hampden-Sydney College, 
      Hampden-Sydney, VA, USA.
FAU - Brandt, John P
AU  - Brandt JP
AD  - Hargadon Laboratory, Department of Biology, Hampden-Sydney College, 
      Hampden-Sydney, VA, USA.
FAU - Hand, Zachary C
AU  - Hand ZC
AD  - Hargadon Laboratory, Department of Biology, Hampden-Sydney College, 
      Hampden-Sydney, VA, USA.
FAU - Ararso, Yonathan T
AU  - Ararso YT
AD  - Hargadon Laboratory, Department of Biology, Hampden-Sydney College, 
      Hampden-Sydney, VA, USA.
FAU - Forrest, Osric A
AU  - Forrest OA
AD  - Hargadon Laboratory, Department of Biology, Hampden-Sydney College, 
      Hampden-Sydney, VA, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150526
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (Chemokines)
RN  - 0 (Immunologic Factors)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cell Count
MH  - *Cell Differentiation
MH  - Chemokines/genetics/metabolism
MH  - Dendritic Cells/*pathology
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques
MH  - Immunologic Factors/metabolism
MH  - Lung/*pathology
MH  - Lymphocyte Activation/immunology
MH  - Macrophages/metabolism
MH  - Melanoma, Experimental/genetics/immunology/*pathology
MH  - Mice, Inbred C57BL
MH  - Spleen/*pathology
MH  - Transforming Growth Factor beta1/metabolism
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2015/05/27 06:00
MHDA- 2016/10/01 06:00
CRDT- 2015/05/27 06:00
PHST- 2014/12/15 00:00 [received]
PHST- 2015/05/05 00:00 [revised]
PHST- 2015/05/20 00:00 [accepted]
PHST- 2015/05/27 06:00 [entrez]
PHST- 2015/05/27 06:00 [pubmed]
PHST- 2016/10/01 06:00 [medline]
AID - icb201558 [pii]
AID - 10.1038/icb.2015.58 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2016 Jan;94(1):24-38. doi: 10.1038/icb.2015.58. Epub 2015 May 
      26.