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    Tumour Tissue Microenvironment Can Inhibit Dendritic Cell Maturation in Colorectal Cancer


    Michielsen, Adriana J. and Hogan, Andrew and Marry, Joseph and Tosetto, Miriam and Cox, Fionnuala and Hyland, John M. and Sheahan, Kieran and O'Donoghue, Diarmuid and Mulcahy, Hugh E. and Ryan, Elizabeth J. and O'Sullivan, Jacintha N. (2011) Tumour Tissue Microenvironment Can Inhibit Dendritic Cell Maturation in Colorectal Cancer. PLoS ONE, 6 (11). e27944. ISSN 1932-6203

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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.

    Item Type: Article
    Additional Information: © 2011 Michielsen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Cite as: Michielsen AJ, Hogan AE, Marry J, Tosetto M, Cox F, et al. (2011) Tumour Tissue Microenvironment Can Inhibit Dendritic Cell Maturation in Colorectal Cancer. PLoS ONE 6(11): e27944. doi:10.1371/journal.pone.0027944
    Keywords: Tumour Tissue; Microenvironment; Inhibit; Dendritic Cell Maturation; Colorectal Cancer;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 12434
    Identification Number: https://doi.org/10.1371/journal.pone.0027944
    Depositing User: Andrew Hogan
    Date Deposited: 17 Feb 2020 16:09
    Journal or Publication Title: PLoS ONE
    Publisher: Public Library of Science
    Refereed: Yes
    Funders: Irish Research Council for Science, Engineering and Technology, Darren Gibbons Foundation
    URI:

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