Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.
AuthorsMichielsen, Adriana J
Hogan, Andrew E
Hyland, John M
Sheahan, Kieran D
O'Donoghue, Diarmuid P
Mulcahy, Hugh E
Ryan, Elizabeth J
O'Sullivan, Jacintha N
AffiliationCentre for Colorectal Disease, St. Vincent's University Hospital, Elm Park, Dublin, Ireland.
Culture Media, Conditioned
Enzyme-Linked Immunosorbent Assay
Intercellular Adhesion Molecule-1
Tissue Culture Techniques
Vascular Endothelial Growth Factor A
MetadataShow full item record
CitationTumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer. 2011, 6 (11):e27944 PLoS ONE
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.
- Inhibition of dendritic cell maturation by the tumor microenvironment correlates with the survival of colorectal cancer patients following bevacizumab treatment.
- Authors: Michielsen AJ, Noonan S, Martin P, Tosetto M, Marry J, Biniecka M, Maguire AA, Hyland JM, Sheahan KD, O'Donoghue DP, Mulcahy HE, Fennelly D, Ryan EJ, O'Sullivan JN
- Issue date: 2012 Aug
- The tumour microenvironment of the upper and lower gastrointestinal tract differentially influences dendritic cell maturation.
- Authors: Morrissey ME, Byrne R, Nulty C, McCabe NH, Lynam-Lennon N, Butler CT, Kennedy S, O'Toole D, Larkin J, McCormick P, Mehigan B, Cathcart MC, Lysaght J, Reynolds JV, Ryan EJ, Dunne MR, O'Sullivan J
- Issue date: 2020 Jun 17
- Effect of oxygen levels on the physiology of dendritic cells: implications for adoptive cell therapy.
- Authors: Futalan D, Huang CT, Schmidt-Wolf IG, Larsson M, Messmer D
- Issue date: 2011 Sep-Oct
- The 30-kDa and 38-kDa antigens from Mycobacterium tuberculosis induce partial maturation of human dendritic cells shifting CD4(+) T cell responses towards IL-4 production.
- Authors: Heuer M, Behlich AS, Lee JS, Ribechini E, Jo EK, Lutz MB
- Issue date: 2013 Oct 3
- [Ag85B and BCG enhance immune activity of dendritic cells in patients with initially treated tuberculosis].
- Authors: Guo Y, Su Y, Sun Y, Guan W, Yang L, Zhang Z, Wang Y, Dai E
- Issue date: 2016 Jun