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

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dc.contributor.author Morrissey, Maria E.
dc.contributor.author Byrne, Róisín
dc.contributor.author Nulty, Celina
dc.contributor.author McCabe, Niamh H.
dc.contributor.author Lynam-Lennon, Niamh
dc.contributor.author Butler, Clare T
dc.contributor.author Kennedy, Susan
dc.contributor.author O'Toole, Dermot
dc.contributor.author Larkin, John
dc.contributor.author McCormick, Paul
dc.contributor.author Mehigan, Brian
dc.contributor.author Cathcart, Mary Clare
dc.contributor.author Lysaght, Joanne
dc.contributor.author Reynolds, John V.
dc.contributor.author Ryan, Elizabeth J.
dc.contributor.author Dunne, Margaret R.
dc.contributor.author O'Sullivan, Jacintha
dc.date.accessioned 2020-06-24T10:05:08Z
dc.date.available 2020-06-24T10:05:08Z
dc.date.issued 2020
dc.identifier.uri http://hdl.handle.net/10344/8951
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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