Induction of dendritic cell maturation in the skin microenvironment by soluble factors derived from colon carcinoma.
Hum Vaccin Immunother
; 10(6): 1622-32, 2014.
Article
in En
| MEDLINE
| ID: mdl-24732313
ABSTRACT
Autologous tumor cell-based vaccines provide a wide range of tumor antigens and personalized neo-epitopes based on individual tumors' unique antigenic mutanome signatures. However, tumor-derived factors may hamper in situ maturation of dendritic cells (DC) and thus interfere with the generation of effective anti-tumor immunity. As the skin is a preferred site for tumor vaccine delivery, we investigated the influence of primary colon carcinoma-derived soluble factors on the maturation state of migrating DC in a human skin explant model. Primary tumor-derived supernatants (TDSN) enhanced the phenotypic maturation state of skin-emigrated DC, resulting in an increased T-cell stimulatory ability in an allogeneic mixed leukocyte response. In case of monocyte-derived DC a similar TDSN-induced maturation induction was found to entirely depend on cyclooxygenase (COX)-regulated prostaglandins. In contrast, the increase in skin-emigrated DC maturation was completely prostaglandin-independent, as evidenced by the inability of the COX inhibitor indomethacin to abrogate this TDSN-induced effect. Although TDSN conditioning affected a drop in IL-12p70 release by the skin-emigrated DC and induced a predominant Th17/Th22 transcriptional profile in subsequently stimulated T-cells, Th cell subset differentiation, as assessed by intracellular cytokine expression upon polyclonal priming and re-stimulation, was not affected. Comparative analysis of phenotypic and transcriptional profiles suggests that the observed maturational effects in skin-derived DC may have been induced by tumor-derived GM-CSF. In conclusion, soluble factors derived from whole-cell colon tumor vaccines will not negatively impact DC migration and maturation in human skin, but rather induce DC maturation that will facilitate the priming of a poly-functional Th cell response.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skin
/
Dendritic Cells
/
Carcinoma
/
Cell Differentiation
/
Cell Movement
/
Colonic Neoplasms
/
Immunologic Factors
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Hum Vaccin Immunother
Year:
2014
Document type:
Article
Affiliation country:
Netherlands