Tumour Tissue Microenvironment Can Inhibit Dendritic Cell Maturation in Colorectal Cancer
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2011Author:
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Michielsen, AJ, Hogan, AE, Marry, J, Tosetto, M, Cox, F, Hyland, JM, Sheahan, KD, O'Donoghue, DP, Mulcahy, HE, Ryan, EJ, O'Sullivan, JN, Tumour Tissue Microenvironment Can Inhibit Dendritic Cell Maturation in Colorectal Cancer, PLOS ONE, 6, 11, 2011, e27944-Download Item:
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.
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Author: O'SULLIVAN, JACINTHA
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PLOS ONE6
11
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Cancer treatment, Colorectal cancer, Cytokines, Dendritic cells, Organism development, Secretion, T cellsDOI:
http://dx.doi.org/10.1371/journal.pone.0027944Metadata
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