Evaluation of immature monocyte-derived dendritic cells generated from patients with colorectal cancer.
Dendritic cells are heterogeneous population of the leukocytes and most potent APC in activation of naive T lymphocytes. Therefore the DCs generated in vitro are under research for their application in anti-tumor immunotherapy. The aim of the study was generation of the immature dendritic cells from peripheral blood monocytes collected from colorectal cancer patients and comparison of their ability to endocytosis, cytokine production and immunophenotype to DCs generated from healthy donors.


METHODS
16 adenocarcinoma stage II patients were included in the study. Dendritic cells were generated in the presence of rhGM-CSF and IL-4. PBMC were isolated from the blood of patients and 16 healthy donors - control group. Immunophenotype, ability of endocytosis of Dextran- FITC as well as intracellular IL-12 expression of the generated dendritic cells was measured using flow cytometry. The cytokines (IL-6, IL-10, IL-12p70, IFN-γ) concentration in the supernatants of DCs culture was measured by ELISA.


RESULTS
The percentage of the immature dendritic cells and expression of CD206 and CD209 antigens was significantly higher in patients group (p <0.05 and p <0.001 respectively). Significantly (p <0.001) higher expression of the antigens which initiate the Th2 immune response (CD80-/CD86 + and B7-H2 + / CD209 +) was in the patients group. There were no differences in endocytosis ability and the cytokines (IL-6, IL-10, IL-12p70, IFN-γ) concentration between investigated groups.


CONCLUSIONS
High immature markers expression on the generated dendritic cells together with identical endocytosis ability in patients group is advantageous in antitumor autologous cells immunotherapy planning. However there is one troubling fact--high expression of markers, which may induce tolerance to particular antigen. It seems to be more reasonable to use the autologous DCs in the antitumor immunotherapy, especially due to the incompatibility in allogenic cells in the context of HLA complex.
Ryszard
R
Maciejewski
Sebastian
S
Radej
Jacek
J
Furmaga
Andrzej
A
Chrościcki
Sławomir
S
Rudzki
Jacek
J
Roliński
Grzegorz
G
Wallner
D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology*; D004705:Endocytosis / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D018664:Interleukin-12 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011956:Receptors, Cell Surface / Q000378:metabolism; D012016:Reference Values; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D016207:Cytokines; D018664:Interleukin-12; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin