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

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...

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Autores principales: Adriana J Michielsen, Andrew E Hogan, Joseph Marry, Miriam Tosetto, Fionnuala Cox, John M Hyland, Kieran D Sheahan, Diarmuid P O'Donoghue, Hugh E Mulcahy, Elizabeth J Ryan, Jacintha N O'Sullivan
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Publicado: Public Library of Science (PLoS) 2011
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Acceso en línea:https://doaj.org/article/1fa55522fd5248f3ba6a2700a7b5a095
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spelling oai:doaj.org-article:1fa55522fd5248f3ba6a2700a7b5a0952021-11-18T07:33:52ZTumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.1932-620310.1371/journal.pone.0027944https://doaj.org/article/1fa55522fd5248f3ba6a2700a7b5a0952011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22125641/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Inflammatory 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.Adriana J MichielsenAndrew E HoganJoseph MarryMiriam TosettoFionnuala CoxJohn M HylandKieran D SheahanDiarmuid P O'DonoghueHugh E MulcahyElizabeth J RyanJacintha N O'SullivanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27944 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Adriana J Michielsen
Andrew E Hogan
Joseph Marry
Miriam Tosetto
Fionnuala Cox
John M Hyland
Kieran D Sheahan
Diarmuid P O'Donoghue
Hugh E Mulcahy
Elizabeth J Ryan
Jacintha N O'Sullivan
Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.
description 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.
format article
author Adriana J Michielsen
Andrew E Hogan
Joseph Marry
Miriam Tosetto
Fionnuala Cox
John M Hyland
Kieran D Sheahan
Diarmuid P O'Donoghue
Hugh E Mulcahy
Elizabeth J Ryan
Jacintha N O'Sullivan
author_facet Adriana J Michielsen
Andrew E Hogan
Joseph Marry
Miriam Tosetto
Fionnuala Cox
John M Hyland
Kieran D Sheahan
Diarmuid P O'Donoghue
Hugh E Mulcahy
Elizabeth J Ryan
Jacintha N O'Sullivan
author_sort Adriana J Michielsen
title Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.
title_short Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.
title_full Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.
title_fullStr Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.
title_full_unstemmed Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.
title_sort tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/1fa55522fd5248f3ba6a2700a7b5a095
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