Morrissey 2016 Europ J Cancer
| Differential dendritic cell inhibition by conditioned media from oesophageal and colorectal cancer. |
» DOI: 10.1016/S0959-8049(16)61758-6
Morrissey M, McCabe N, Dunne M, O'Sullivan J (2016) Europ J Cancer
Abstract: Oesophageal adenocarcinoma (OAC) has one of the worst prognosis of all cancers and its incidence is increasing. Chemoradiation therapy (CRT) followed by surgery is the standard of care for locally advanced tumours, however good response rates are only achieved for about one quarter of patients. The ability of dendritic cells (DCs) to stimulate an effective immune response can be highly compromised in cancer patients through unknown mechanisms. Tumours inhibit dendritic cell maturation and function in order to evade host immunity, which has been demonstrated in colorectal cancer.
Monocyte-derived dendritic cells (MDDC) were treated for 4 hours with conditioned media from patient tumour explants or cell lines followed by overnight stimulation with LPS. Following this, flow cytometry was performed for DC maturation markers (CD40, CD80, CD86, CD83, CD11c, CD54 and HLA-DR) and IL12 p70 ELISAs were performed on DC supernatants.
Conditioned media from OAC cancer cell lines inhibit DC maturation markers following 2 Gy irradiation. This inhibition is more pronounced using the radioresistant isogenic line compared to the parental line. However, conditioned media from irradiated or unirradiated OAC treatment-naıve biopsies (n = 33) do not inhibit DC maturation markers. Levels of IL12 p70 and other cytokines indicates there is inhibition of DC secreted factors. In contrast, conditioned media from resected colonic tumours cause DC inhibition with a significant reduction in LPS-induced upregulation of CD54 and CD83 (CRC TCM n = 8).
In conclusion, we observe differences in DC inhibition between upper and lower GI cancers. Further investigation to understand if DC modulation is a factor in responsiveness of oesophageal cancer to CRT is required.
• Bioblast editor: Bufe A
Labels:
Pathology: Cancer
Organism: Human Tissue;cell: Nervous system
Affiliation
Trinity College Dublin- St James’s Hospital, Dept Surgery, Dublin, Ireland
