Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

Hdl Handle:
http://hdl.handle.net/10147/218993
Title:
Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.
Authors:
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; O'Sullivan, Jacintha N
Affiliation:
Centre for Colorectal Disease, St. Vincent's University Hospital, Elm Park, Dublin, Ireland.
Citation:
Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer. 2011, 6 (11):e27944 PLoS ONE
Journal:
PloS one
Issue Date:
2011
URI:
http://hdl.handle.net/10147/218993
DOI:
10.1371/journal.pone.0027944
PubMed ID:
22125641
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
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
ISSN:
1932-6203
Ethical Approval:
N/A

Full metadata record

DC FieldValue Language
dc.contributor.authorMichielsen, Adriana J-
dc.contributor.authorHogan, Andrew E-
dc.contributor.authorMarry, Joseph-
dc.contributor.authorTosetto, Miriam-
dc.contributor.authorCox, Fionnuala-
dc.contributor.authorHyland, John M-
dc.contributor.authorSheahan, Kieran D-
dc.contributor.authorO'Donoghue, Diarmuid P-
dc.contributor.authorMulcahy, Hugh E-
dc.contributor.authorRyan, Elizabeth J-
dc.contributor.authorO'Sullivan, Jacintha N-
dc.date.accessioned2012-04-18T11:50:22Z-
dc.date.available2012-04-18T11:50:22Z-
dc.date.issued2011-
dc.identifier.citationTumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer. 2011, 6 (11):e27944 PLoS ONE-
dc.identifier.issn1932-6203-
dc.identifier.pmid22125641-
dc.identifier.doi10.1371/journal.pone.0027944-
dc.identifier.urihttp://hdl.handle.net/10147/218993-
dc.description.abstractInflammatory 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.-
dc.language.isoen-
dc.rightsArchived with thanks to PloS oneen_GB
dc.subject.meshAged-
dc.subject.meshAntigens, CD-
dc.subject.meshAntigens, CD86-
dc.subject.meshCell Differentiation-
dc.subject.meshCells, Cultured-
dc.subject.meshChemokine CCL2-
dc.subject.meshChemokine CXCL1-
dc.subject.meshChemokine CXCL5-
dc.subject.meshCoculture Techniques-
dc.subject.meshColorectal Neoplasms-
dc.subject.meshCulture Media, Conditioned-
dc.subject.meshDendritic Cells-
dc.subject.meshEnzyme-Linked Immunosorbent Assay-
dc.subject.meshFemale-
dc.subject.meshFlow Cytometry-
dc.subject.meshHLA-DR Antigens-
dc.subject.meshHumans-
dc.subject.meshImmunoglobulins-
dc.subject.meshIntercellular Adhesion Molecule-1-
dc.subject.meshInterferon-gamma-
dc.subject.meshLipopolysaccharides-
dc.subject.meshMale-
dc.subject.meshMembrane Glycoproteins-
dc.subject.meshTissue Culture Techniques-
dc.subject.meshTumor Microenvironment-
dc.subject.meshVascular Endothelial Growth Factor A-
dc.titleTumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.en_GB
dc.contributor.departmentCentre for Colorectal Disease, St. Vincent's University Hospital, Elm Park, Dublin, Ireland.-
dc.identifier.journalPloS one-
dc.type.qualificationlevelN/Aen
cr.approval.ethicalN/Aen
dc.description.provinceLeinsteren

Related articles on PubMed

All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.