Type

Journal Article

Authors

E J Ryan
G A Doherty
J O'Sullivan
D O'Donoghue
D Fennelly
P R O'Connell
J M Hyland
D C Winter
H E Mulcahy
K Sheahan
and 4 others

Subjects

Microbiology

Topics
male monocytes interleukin 12 colorectal neoplasms immunosuppression tumor microenvironment middle aged adult inflammation aged humans dendritic cells aged 80 and over stat3 protein human immunology female stat3 transcription factor interleukin 10 lipopolysaccharides

Tumour microenvironment of both early- and late-stage colorectal cancer is equally immunosuppressive. (2014)

Abstract Tumour microenvironment (TME) of advanced colorectal cancer (CRC) suppresses dendritic cell (DC) maturation. Here, our aim was to determine how the microenvironment of early-stage tumours influences DCs. Tumour-conditioned media (TCM) was generated by culturing explant tumour tissue in vitro (n=50). Monocyte-derived DCs (MDDCs) of healthy donors or cancer patients were pretreated with TCM and stimulated with lipopolysaccharide (LPS). DC maturation was assessed by flow cytometry and cytokine production measured by ELISA. TCM from both early- and late-staged tumours abrogated LPS-induction of IL-12p70 secretion, while increasing IL-10. The profile of inflammatory mediators in TCM was similar across stages, and all increased pSTAT3 expression by DCs.CRC patient DCs (n=31) secreted low levels of IL-12p70 and failed to upregulate expression of maturation markers in response to LPS. Furthermore, in vitro culture of autologous DCs with TCM did not change the hypo-responsiveness of patient DCs. Our data demonstrates that the TME of all stages of CRC contains inflammatory mediators capable of suppressing local DCs. MDDCs obtained from CRC patients are hyporesponsive to stimuli such as LPS. Measures to reverse the negative influence of the TME on DCs will optimise cancer vaccines in both early- and late-stage CRC.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

E J Ryan, G A Doherty, J O'Sullivan, D O'Donoghue, D Fennelly, P R O'Connell, J M Hyland, D C Winter, H E Mulcahy, K Sheahan and 4 others

Experts in our system

1
Elizabeth J Ryan
University College Dublin
 
2
Glen A Doherty
University College Dublin
Total Publications: 57
 
3
Jacintha O'Sullivan
Trinity College Dublin
Total Publications: 74
 
4
Diarmuid O'Donoghue
University College Dublin
Total Publications: 42
 
5
David Fennelly
Trinity College Dublin
Total Publications: 11
 
6
P R O'Connell
University College Dublin
Total Publications: 75
 
7
John Hyland
Dublin Business School
Total Publications: 47
 
8
Desmond C. Winter
University College Dublin
Total Publications: 53
 
9
Hugh E Mulcahy
University College Dublin
Total Publications: 43
 
10
Kieran Sheahan
University College Dublin
Total Publications: 40