TY - JOUR
T1 - The tumour microenvironment of the upper and lower gastrointestinal tract differentially influences dendritic cell maturation
AU - Morrissey, Maria E.
AU - Byrne, Róisín
AU - Nulty, Celina
AU - McCabe, Niamh H.
AU - Lynam-Lennon, Niamh
AU - Butler, Clare T.
AU - Kennedy, Susan
AU - O'Toole, Dermot
AU - Larkin, John
AU - McCormick, Paul
AU - Mehigan, Brian
AU - Cathcart, Mary Clare
AU - Lysaght, Joanne
AU - Reynolds, John V.
AU - Ryan, Elizabeth J.
AU - Dunne, Margaret R.
AU - O'Sullivan, Jacintha
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2020/6/17
Y1 - 2020/6/17
N2 - 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.
AB - 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.
KW - Dendritic cell inhibition
KW - Gastrointestinal cancer
KW - Radiotherapy
KW - TNF-α
KW - Tumour conditioned media
KW - Tumour microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85086692659&partnerID=8YFLogxK
U2 - 10.1186/s12885-020-07012-y
DO - 10.1186/s12885-020-07012-y
M3 - Article
C2 - 32552799
AN - SCOPUS:85086692659
SN - 1471-2407
VL - 20
JO - BMC Cancer
JF - BMC Cancer
IS - 1
M1 - 566
ER -
