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

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posted on 2020-06-24, 10:05 authored by Maria E. Morrissey, Róisín Byrne, Celina Nulty, Niamh H. McCabe, Niamh Lynam-Lennon, Clare T Butler, Susan Kennedy, Dermot O'Toole, John Larkin, Paul McCormick, Brian Mehigan, Mary Clare Cathcart, Joanne Lysaght, John V. Reynolds, Elizabeth J. Ryan, Margaret R. Dunne, Jacintha O'Sullivan
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.

History

Publication

BMC Cancer;20,566

Publisher

BMC

Note

peer-reviewed

Other Funding information

Irish Cancer Society

Language

English

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