The tumour microenvironment of the upper and lower gastrointestinal tract differentially influences dendritic cell maturation.
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2020Access:
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Morrissey, M.E., Byrne, R., Nulty, C., McCabe, N.H., Lynam-Lennon, N., Butler, C.T., Kennedy, S., O'Toole, D., Larkin, J., McCormick, P., Mehigan, B., Cathcart, M.C., Lysaght, J., Reynolds, J.V., Ryan, E.J., Dunne, M.R., O'Sullivan, J., The tumour microenvironment of the upper and lower gastrointestinal tract differentially influences dendritic cell maturation, BMC Cancer. 2020 Jun 17;20(1):566Download Item:
Abstract:
Background: Only 10-30% of oesophageal and rectal adenocarcinoma patients treated with neoadjuvant chemoradiotherapy have a complete pathological response. Inflammatory and angiogenic mediators in the tumour microenvironment (TME) may enable evasion of anti-tumour immune responses.
Methods: The TME influence on infiltrating dendritic cells (DCs) was modelled by treating immature monocyte-derived DCs with Tumour Conditioned Media (TCM) from distinct gastrointestinal sites, prior to LPS-induced maturation.
Results: Cell line conditioned media from gastrointestinal cell lines inhibited LPS-induced DC markers and TNF-α secretion. TCM generated from human tumour biopsies from oesophageal, rectal and colonic adenocarcinoma induced different effects on LPS-induced DC markers - CD54, CD80, HLA-DR, CD86 and CD83 were enhanced by oesophageal cancer; CD80, CD86 and CD83 were enhanced by rectal cancer, whereas CD54, HLA-DR, CD86, CD83 and PD-L1 were inhibited by colonic cancer. Notably, TCM from all GI cancer types inhibited TNF-α secretion. Additionally, TCM from irradiated biopsies inhibited DC markers. Profiling the TCM showed that IL-2 levels positively correlated with maturation marker CD54, while Ang-2 and bFGF levels negatively correlated with CD54.
Conclusion: This study identifies that there are differences in DC maturational capacity induced by the TME of distinct gastrointestinal cancers. This could potentially have implications for anti-tumour immunity and response to radiotherapy.
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http://people.tcd.ie/jlysaghthttp://people.tcd.ie/reynoljv
http://people.tcd.ie/dunnem12
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BMC Cancer;20;
1;
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Dendritic Cells, Cancer Vaccines, Immunotherapy, Dendritic cell inhibition, Gastrointestinal cancer, Radiotherapy, TNF-α, Tumour conditioned media, Tumour microenvironmentDOI:
http://dx.doi.org/10.1186/s12885-020-07012-yISSN:
1471-2407Metadata
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