Dataset Information

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

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-? 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-? 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.

SUBMITTER: Morrissey ME

PROVIDER: S-EPMC7302160 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Morrissey Maria E ME Byrne Róisín R Nulty Celina C McCabe Niamh H NH Lynam-Lennon Niamh N Butler Clare T CT Kennedy Susan S O'Toole Dermot D Larkin John J McCormick Paul P Mehigan Brian B Cathcart Mary-Clare MC Lysaght Joanne J Reynolds John V JV Ryan Elizabeth J EJ Dunne Margaret R MR O'Sullivan Jacintha J

BMC cancer 20200617 1

<h4>Background</h4>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.<h4>Methods</h4>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 L ...[more]

PMID: 32552799

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Project description:The microbiota of the bovine upper respiratory tract has been recently characterized, but no data for the lower respiratory tract are available. A major health problem in bovine medicine is infectious bronchopneumonia, the most common respiratory syndrome affecting cattle. With this study, we used 16S rRNA gene sequencing to characterize and compare the microbial community composition of the upper and lower respiratory tracts in calves.The microbiota of the upper (nasal swab [NS]) and the lower (trans-tracheal aspiration [TTA]) respiratory tracts of 19 post-weaned Piedmontese calves with (8/19) and without (11/19) clinical signs of respiratory disease, coming from six different farms, was characterized by 16S rRNA gene metabarcoding. A total of 29 phyla (29 in NS, 21 in TTA) and 305 genera (289 in NS, 182 in TTA) were identified. Mycoplasma (60.8%) was the most abundant genus identified in both the NS (27.3%) and TTA (76.7%) samples, followed by Moraxella (16.6%) in the NS and Pasteurella (7.3%) in the TTA samples. Pasteurella multocida (7.3% of total operational taxonomic units [OTUs]) was the most abundant species in the TTA and Psychrobacter sanguinis (1.1% of total OTUs) in the NS samples. Statistically significant differences between the NS and the TTA samples were found for both alpha (Shannon index, observed species, Chao1 index, and Simpson index; P?=?0.001) and beta (Adonis; P?=?0.001) diversity. Comparison of the NS and TTA samples by farm origin and clinical signs revealed no statistical difference (P?>?0.05), except for farm origin for the NS samples when compared by the unweighted UniFrac metric (P?=?0.05).Using 16S rRNA gene sequencing, we characterized the microbiota of the upper and lower respiratory tracts of calves, both healthy individuals and those with clinical signs of respiratory disease. Our results suggest that environmental factors may influence the composition of the upper airway microbiota in cattle. While the two microbial communities (upper and lower airways) differed in microbial composition, they shared several OTUs, suggesting that the lung microbiota may be a self-sustaining, more homogeneous ecosystem, influenced by the upper respiratory tract microbiota.

Dataset Information

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

Publications

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

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