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The tumour microenvironment of the upper and lower gastrointestinal tract differentially influences dendritic cell maturation

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Show simple item record Morrissey, Maria E. Byrne, Róisín Nulty, Celina McCabe, Niamh H. Lynam-Lennon, Niamh Butler, Clare T Kennedy, Susan O'Toole, Dermot Larkin, John McCormick, Paul Mehigan, Brian Cathcart, Mary Clare Lysaght, Joanne Reynolds, John V. Ryan, Elizabeth J. Dunne, Margaret R. O'Sullivan, Jacintha 2020-06-24T10:05:08Z 2020-06-24T10:05:08Z 2020
dc.description peer-reviewed en_US
dc.description.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. en_US
dc.language.iso eng en_US
dc.publisher BMC en_US
dc.relation CRF13MOR en_US
dc.relation.ispartofseries BMC Cancer;20,566
dc.subject Gastrointestinal cancer en_US
dc.subject Dendritic cell inhibition en_US
dc.subject Tumour conditioned media en_US
dc.title The tumour microenvironment of the upper and lower gastrointestinal tract differentially influences dendritic cell maturation en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.identifier.doi 10.1186/s12885-020-07012-y
dc.contributor.sponsor Irish Cancer Society en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US

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