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Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.
Michielsen, Adriana J Hogan, Andrew E Marry, Joseph Tosetto, Miriam Cox, Fionnuala Hyland, John M Sheahan, Kieran D O'Donoghue, Diarmuid P Mulcahy, Hugh E Ryan, Elizabeth J
Michielsen, Adriana J
Hogan, Andrew E
Marry, Joseph
Tosetto, Miriam
Cox, Fionnuala
Hyland, John M
Sheahan, Kieran D
O'Donoghue, Diarmuid P
Mulcahy, Hugh E
Ryan, Elizabeth J
Advisors
Editors
Other Contributors
Date
2011
Date Submitted
Keywords
Other Subjects
Subject Mesh
Aged
Antigens, CD
Antigens, CD86
Cell Differentiation
Cells, Cultured
Chemokine CCL2
Chemokine CXCL1
Chemokine CXCL5
Coculture Techniques
Colorectal Neoplasms
Culture Media, Conditioned
Dendritic Cells
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
HLA-DR Antigens
Humans
Immunoglobulins
Intercellular Adhesion Molecule-1
Interferon-gamma
Lipopolysaccharides
Male
Membrane Glycoproteins
Tissue Culture Techniques
Tumor Microenvironment
Vascular Endothelial Growth Factor A
Antigens, CD
Antigens, CD86
Cell Differentiation
Cells, Cultured
Chemokine CCL2
Chemokine CXCL1
Chemokine CXCL5
Coculture Techniques
Colorectal Neoplasms
Culture Media, Conditioned
Dendritic Cells
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
HLA-DR Antigens
Humans
Immunoglobulins
Intercellular Adhesion Molecule-1
Interferon-gamma
Lipopolysaccharides
Male
Membrane Glycoproteins
Tissue Culture Techniques
Tumor Microenvironment
Vascular Endothelial Growth Factor A
Planned Date
Start Date
Collaborators
Principal Investigators
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TumourTissue.pdf
Adobe PDF, 621.9 KB
Alternative Titles
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Abstract
Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5) could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.
Language
en
ISSN
1932-6203
eISSN
ISBN
DOI
10.1371/journal.pone.0027944
PMID
22125641
PMCID
Sponsorships
Funding Sources
Funding Amounts
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Methodology
Duration
Ethical Approval
N/A